This post hoc analysis of patients from the AVERT trial evaluated data from 447 patients with inherited thrombophilia who also had ambulatory cancer that put them at moderate-to-high risk of VTE. All patients were undergoing chemotherapy.

The median age of the cohort at baseline was 62 and 43% of patients were male. There were 36.9% and 50.7% of patients with or without VTE taking apixaban. There were 4.5% of patients harboring a FVL mutation and 60.4% with a non-O blood type.

There were 39 patients who developed VTE and 39 who experienced bleeding. An FVL mutation was significantly associated with higher odds of VTE (odds ratio [OR], 5.24; 95% CI, 1.86-14.70; P =.0017). A non-O blood type was also associated with an increased risk of developing VTE (OR, 2.72; 95% CI, 1.22-6.08; P =.0144).

The presence of mutation sin FII, FXI, fibrinogen gamma, serpin family A member 10, and FV at K858R were not associated with an increased risk of VTE. None of the mutations evaluated, including in FVL, and none of the ABO blood types were associated with a risk of bleeding.

The risk of VTE was completely mitigated among patients with an FVL mutation who received prophylactic anticoagulation. The risk was also mitigated among patients with a non-O blood type, but to a lesser extent.

“Our study indicated that an FVL mutation and non-O blood types are associated with an increased risk of VTE in intermediate to high-risk ambulatory cancer patients receiving chemotherapy, and these patients benefitted from prophylactic anticoagulation with a low risk of bleeding,” the authors concluded in their report.

Disclosures: The study was supported in part by Bristol Myers Squibb and Pfizer. Please see the original reference for a full list of disclosures.

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Compared with warfarin, direct oral anticoagulant (DOAC) treatment is associated with a lower risk of recurrent venous thromboembolism (VTE) in patients taking extended anticoagulation treatment for VTE, according to research published in JAMA Network Open.

Researchers conducted a retrospective cohort study to compare rates of recurrent VTE, hospitalizations for hemorrhage, and all-cause death among adults prescribed DOACs or warfarin whose anticoagulant treatment was extended beyond 6 months after acute VTE.

Patients received a diagnosis of incident VTE between 2010 and 2018 at 2 integrated health care delivery systems in California and completed at least 6 months of oral anticoagulant treatment with DOACs or warfarin. They were followed from the end of the initial 6-month anticoagulant treatment period until discontinuation of treatment, occurrence of an outcome event, health plan disenrollment, or end of the study follow-up period (December 31, 2019).

The study included a total of 18,495 patients (29.6% ≥75 years of age; 51.5% men), 2134 (11.5%) receiving DOAC therapy and 16 361 (88.5%) receiving warfarin therapy.

The analysis demonstrated lower unadjusted event rates in patients receiving DOAC therapy than warfarin therapy for recurrent VTE (2.92 vs 4.14 per 100 person-years), hospitalizations for hemorrhage (1.02 vs 1.81 per 100 person-years), and all-cause death (3.79 vs 5.40 per 100 person-years).

After multivariable adjustment, DOACs continued to be associated with a significantly lower risk of recurrent VTE (adjusted hazard ratio [aHR], 0.66; 95% CI, 0.52-0.82), but the risks of hospitalization for hemorrhage (aHR, 0.79; 95% CI, 0.54-1.17) and all-cause death (aHR, 0.96; 95% CI, 0.78-1.19) were not significantly different than those of patients receiving warfarin treatment.

“Our study contributes to the growing evidence supporting the use of DOACs for both initial and extended treatment of VTE in terms of clinical outcomes as well as treatment satisfaction,” the study authors wrote in their report.

Limitations of the study included the retrospective nature, nonrandomization of patients to the anticoagulant treatments, and a lack of a definitive date of or reason for discontinuation of therapy.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 

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The incidence of recurrence among patients with first-time cancer-associated venous thromboembolism was 5.2% in the first 6 months and 6.7% at 1 year.

Researchers evaluated the risk of recurrent venous thromboembolism with cancer-specific factors among Danish patients with active cancer and first-time venous thromboembolism. Data were obtained from nationwide databases with prospective information from the Danish health care system.

Patients aged 18 years and older with active cancer and venous thromboembolism and residing in Denmark between 2003 and 2018 were identified in the Danish National Patient Registry. Participants who survived the first 10 days after their first-time venous thromboembolism diagnosis were followed to the first subsequent diagnosis of venous thromboembolism, death, emigration from Denmark, or end of 2018, whichever came first. The analyses were reported at 6 months and 1 year.

The cohort included 34,072 patients (53% female; median age, 72 years). Among the participants, 16% were diagnosed with brain cancer, 11% with gastrointestinal cancer, 10% with breast cancer, 7.8% with lung cancer, 6.5% with hematologic cancer, 6.4% with gynecologic cancer, 4.6% with genitourinary cancer, and 37% with other cancer types. Deep vein thrombosis was diagnosed in 55% of the cohort, 45% had pulmonary embolism, and 2.6% had both diagnoses.

A total of 1755 recurrent venous thromboembolic events occurred within 1 year, of which 1352 were diagnosed within the initial 6 months of follow-up. The risk of recurrence was 5.1% at 6 months and increased to 6.7% at 1 year. The overall mortality risk was 26% at 6 months and 36% at 1 year, with the highest risk occurring in patients with lung cancer at 6 months and 1 year.

The recurrence risk after 6 months was comparable for men and women (5.2% and 4.9%, respectively) and among Ottawa risk score groups: 5.0% for low risk and 5.1% for high risk (subdistribution hazard ratio, 1.12; 95% CI, 0.97-1.30). Recurrence risks were 4.7% for localized stage cancer and 6.3% for distant cancers, and they were similar during follow-up with surgery (5.3%) and anticancer treatment (5.1% for chemotherapy, 5.0% for radiotherapy, 4.5% for endocrine therapy, and 5.4% for immunotherapy at 6 months).

The risks were 6.5% for patients with genitourinary cancer, 6.1% for lung cancer, 5.6% for gastrointestinal cancer, 5.2% for brain cancer, 5.1% for hematologic cancer, 4.7% for gynecologic cancer, 4.1% for breast cancer, and 4.8% for other cancer types, compared with the overall cohort risk of recurrence of 5.2% at 6 months.

Among several limitations, the datasets did not include information on sociocultural determinants of health such as race/ethnicity and lifestyle, and complete information was unavailable regarding cancer stage for all patients and cancer progression during follow-up. Data were also unavailable for site of first-time deep venous thrombosis and whether some venous thromboembolisms were incidentally diagnosed, for example, during routine scans for cancer, which may affect patients differently for age and cancer stage.

“Refining risk stratification for recurrence may improve decision-making regarding treatment duration after cancer-associated thromboembolism and ultimately lead to improvements in the net clinical benefit from anticoagulant treatment in this challenging patient population,” concluded the researchers.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures

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The researchers evaluated data from TE-related hospitalizations in patients with PV who had inpatient discharges from January 1, 2017, through June 30, 2020, with records obtained using the PINC AI^TM Healthcare Database.

At index hospitalization, patients had experienced a venous thromboembolism (VTE), arterial thromboembolism (ATE), or both. The main outcomes of interest in this study were HCRU and costs associated with TE-related hospitalizations, at both the index TE hospitalization and in the 2 years after index discharge.

There were 3494 patients included in the study, of whom 947 had VTE only, 2416 had ATE only, and 131 had both. The mean patient age overall was 70.7 years (SD, 14.0), and the mean Charlson Comorbidity Index score was 3.2 (SD, 2.3). The majority of patients (72.6%) had Medicare.

In patients with VTE only, deep vein thrombosis was the most common (74.0%) thromboembolic event, followed by pulmonary embolism (43.4%) and superficial TE (5.3%). In patients with ATE only, ischemic stroke was the most common (63.0%) event, followed by myocardial infarction (34.3%), transient ischemic attack (6.6%), and peripheral thrombosis (1.6%).

Overall, the mean total hospitalization cost was $24,403 (in 2021 USD) during the index TE hospitalization, with a mean hospital length of stay of 7 days (SD, 9). Patients with both ATEs and VTEs had the highest mean total hospitalization cost, at $47,079. Mean total hospitalization costs were $28,391 for patients with VTE only and $21,606 for those with ATE only.

Approximately one-third of patients overall had been admitted into an intensive care unit (ICU), and their mean ICU cost was $29,342. The mean ICU cost was highest for patients with both ATE and VTE ($39,560) and lowest for patients with ATE only ($26,209).

TE-related hospital readmissions also increased over time. In the overall population, with 2 years of follow-up the readmission risk was calculated to be 20.0%. Mean overall costs during the index visit, in combination with TE-related readmissions over the 2-year follow-up, were calculated to be $30,285 overall, and were as high as $53,998 for patients who had experienced both ATE and VTE at index.

The all-cause in-hospital mortality rate for the overall population was 6.2% during the index hospitalization, and it was as high as 12.2% for patients who had both ATE and VTE at index. In the overall population, the all-cause in-hospital mortality rate during the 2-year follow-up after the index visit was an additional 4.7%, and as high as 11.5% for those with both ATE and VTE at index.

In this study, the researchers concluded that patients with PV showed high HCRU, costs, and mortality with TE-related hospitalizations. They also noted the importance of preventing TE in patients with PV.

Disclosures: This research was supported by Incyte Corporation. Please see the original reference for a full list of disclosures.

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The double-blind, placebo-controlled MACiTEPH study (ClinicalTrials.gov Identifier: NCT04271475) was assessing the safety and efficacy of macitentan, an endothelin receptor antagonist, in patients with inoperable or persistent/recurrent CTEPH (WHO Group IV). Patients were randomly assigned to receive either mactentan 75mg or placebo orally once daily. The primary endpoint was the change from baseline to week 28 in 6-minute walk (6MW) distance, as measured by the 6MW test.

An analysis of interim data led the study’s independent data monitoring committee to recommend ending the trial. There were no new safety issues reported.

While the MACiTEPH trial has been discontinued, the Company noted that the phase 3 UNISUS study (ClinicalTrials.gov Identifier: NCT04273945), which is assessing macitentan 75mg in patients with pulmonary arterial hypertension (PAH), will continue as planned.

Macitentan is currently approved under the brand name Opsumit in a 10mg strength for the treatment of PAH (WHO Group I) to reduce the risks of disease progression and hospitalization for PAH.

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Investigators aimed to validate use of the aGAPSS, Padua score, and Caprini score for prediction of thrombosis recurrence among patients with APS.

A single-center prospective cohort study was conducted, including patients with APS who had a known history of thrombotic events at the time of diagnosis. The primary study endpoint was the first recurrence of venous or arterial thrombosis. Thromboses were confirmed by imaging and physician diagnosis.

Cox regression analysis and the Harrell c-index were used to validate the 3 prediction models.

A total of 362 patients were included in the study. Mean patient age was 36.3 years, 57.7% were women, and median follow-up was 2.32 years.

Patients presented with a total of 53 (14.6%) recurrent thrombotic events during the follow-up period, of which 32 were venous (8.84%) and 21 were arterial (5.80%). None of these recurrences were fatal.

Overall thrombosis risk was 5.0%, 14.3%, and 17.9% at years 1, 3, and 5, respectively. Venous and arterial thrombosis risks at years 1, 3, and 5 were 3.8% and 1.6%, 9.9% and 5.6%, and 12.8% and 6.9%, respectively

At the time of venous thrombosis diagnosis, 37.5% of patients received inadequate anticoagulation, compared with 47.6% of patients diagnosed with arterial thrombosis.

The Harrell c-index for thrombosis prediction was 0.54 (95% CI, 0.44-0.64) for aGAPSS, 0.54 (95% CI, 0.46-0.62) for the Padua score, and 0.50 (95% CI, 0.42-0.58) for the Caprini score.

The best predictor of venous thrombosis was the Padua score (Harrell c-index, 0.61; 95% CI, 0.53-0.69). The best predictor of arterial thrombosis was aGAPSS (Harrell’s C index 0.61; 95% CI, 0.47-0.75).

Study limitations included differing anticoagulation practices at the study site vs other centers and missing data on patient drug adherence, which could potentially influence thrombosis recurrence. Additionally, data on antiphospholipid antibody positivity was not validated due to the small sample size for thrombosis recurrence.

The study authors concluded, “The construction of new prediction models respectively for venous and arterial thrombosis recurrence in APS patients is required to guide treatment.”

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Investigators assessed MACE risk among patients with RA treated with opioids vs NSAIDs.

A new-user comparator cohort study was conducted using data from FORWARD, The National Databank for Rheumatic Diseases. Adult patients with RA who had no previous cancer diagnoses and participated in FORWARD between January 1998 and December 2021 were included in the analysis. Patients who initiated opioids were matched 1:2 with those who initiated NSAIDs.  

Primary study outcomes included all-cause mortality and incident MACE as a composite endpoint for fatal or nonfatal myocardial infarction, stroke, heart failure, VTE or cardiovascular disease mortality.

Of the 6866 patients who initiated opioids, 212 experienced MACE at a rate of 20.6 events/1000 person-years (PYs), while 253 of the 13,689 patients who initiated NSAIDs experienced MACE at a rate of 18.9 events/1000 PYs.

At 13 months of follow-up, a total of 144 deaths occurred among patients taking opioids, corresponding to a rate of 13.5 deaths/1000 PYs. Similarly, 150 deaths occurred among patients taking NSAIDs, corresponding to a rate of 10.8 deaths/1000 PYs.

The risk for MACE was similar among patients initiating opioids or NSAIDs (hazard ratio [HR], 1.02; 95% CI, 0.85-1.22), but all-cause mortality was 33% higher among those initiating opioids vs NSAIDs (HR, 1.33; 95% CI, 1.06-1.67).

Among the specific MACE outcomes, patients initiating opioids were at greater risk for VTE compared with those initiating NSAIDs (HR, 1.41; 95% CI, 0.84-2.35).

Of the patients initiating opioids, 81% and 19% were taking weak and strong opioids, respectively. Both weak (HR, 1.51; 95% CI, 1.18-1.92) and strong (HR, 2.07; 95% CI, 1.40-3.05) opioids were associated with increased risk for all-cause mortality.

Weak (HR, 1.55; 95% CI, 1.00-4.19) and strong (HR, 2.16; 95% CI, 0.63-7.44) opioids were also associated with increased risk for VTE.

However, these increased risks were greater among patients taking strong opioids, which may indicate a dose-dependent relationship.

Among several study limitations, misclassification of drug groups was possible due to patients’ self-reporting. Additionally, the effects of opioid dose and duration on outcomes were not assessed due to inadequate data. Finally, samples for individual outcomes of MACE were likely underpowered.

The study authors concluded, “These adverse effects of opioids, along with previously reported increased risk of serious infection, fracture and delay in [disease-modifying antirheumatic drug] initiation, have important clinical implications for reducing the opioid epidemic that has not spared those with RA.”

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Investigators sought to assess the efficacy and safety of protamine for heparin reversal in PCI. Stent thrombosis was the primary endpoint. Mortality, major bleeding complications, and hospitalization length of stay were secondary endpoints.

The investigators conducted a systematic review and meta-analysis searching the Cochrane, Embase, and PubMed databases from inception through most of April 2023. The search included randomized controlled trials (RCTs) or cohort studies published in English that examined protamine as the intervention in any PCI.

There were11 studies included in the analysis, of which 2 were RCTs (n=316) and the others were not randomized, with 1 dissertation. It is unclear if the data in the dissertation manuscript was the same data as in the associated abstract. This study was included in the analysis nonetheless, however it was excluded in the sensitivity analysis.

Among the 9 nonrandomized studies, 3 were rated poor quality based on the Newcastle Ottawa Quality Assessment for cohort studies and subsequently excluded during sensitivity analysis. Among the 2 RCTs, 1 was rated fair using the Cochrane risk of bias assessment tool and the other had an unclear risk of selection bias and reporting bias, however current review authors believed these biases did not affect the outcome and subsequently rated the quality of this RCT as fair.

The pooled analysis included almost 14,991 patients, of which 9541 had procedures with protamine and 5450 had procedures without protamine. Among 9 of the included studies, stent thrombosis was defined 3 different ways, and the remaining 2 studies failed to define stent thrombosis. Between studies, the time frame for stent thrombosis was inconsistent, ranging from within 24 hours after PCI to more than 1 year after PCI, and some of the studies failed to mention time frame.

Investigators found no association between protamine and stent thrombosis (odds ratio [OR], 0.58; 95% CI, 0.33-1.01; P =.05) and no association between protamine and mortality (OR, 0.94; 95% CI, 0.42-2.13; P =.89).

Protamine was associated with decreased incidence of major bleeding complications (OR, 0.48; 95% CI, 0.25-0.95; P =.03), and protamine was associated with decreased length of hospitalization, however this outcome was associated with significant heterogeneity.

Limitations of the study include the RCTs being older studies predating newer generation drug-eluting stents thus limiting generalizability of findings.

“In patients pretreated with dual antiplatelet therapy (DAPT), protamine may be a safe and efficacious option to facilitate earlier sheath removal, reduce major bleeding complications, and reduce length of hospitalization without increased risk of stent thrombosis,” the investigators wrote. “Protamine should not be withheld when major bleeding events occur in PCI as the risk of stent thrombosis appears to be minimal and no more than that of patients not receiving protamine.”

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For this US-based retrospective analysis, the research team used data from the National Inpatient Sample. Included patients had PNH, based on diagnosis codes, and admissions during the period of 2016 through 2019. Admissions related to a variety of other hypercoagulable conditions were excluded. In their analyses, the researchers evaluated data regarding inpatient characteristics, outcomes, and VTE-related complications.

A total of 3600 hospitalizations were included in the analysis. Of these, 9.6% were related to VTE. Most commonly, VTE involved lower extremity deep vein thrombosis (DVT), which reflected 29% of VTE-related cases.

Among other VTE-related cases, hepatic vein thrombosis/Budd Chiari syndrome was associated with 23.2%, portal vein thrombosis with 20.3%, pulmonary embolism with 17.4%, upper extremity DVT with 17.4%, nonspecific VTE with 4.3%, and renal vein thrombosis with 1.5%.

All-cause inpatient mortality rates were similar with VTE (1.4%) and without VTE (2.5%; P =.24). Hospitalizations involving VTE-related complications showed significant associations with other outcomes, however, compared with hospitalizations not involving VTE-related complications. These included a longer mean length of stay (10 days versus 6.3 days; P <.001), a greater mean cost of hospitalizations ($178,143 versus $100,547; P <.001), and a lower rate of patients discharged to home (66.7% versus 72.5%; P =.02).

In patients included in this study, VTE was associated with a younger age and higher prevalence of comorbid obesity and chronic liver disease. Myelodysplastic syndrome and aplastic anemia were less common in the patients with VTE, but the researchers noted in their report that relationships between these diagnoses and VTE risk need to be assessed using prospective clinical data.

The researchers concluded that this study suggests a possibility that many patients may either not have access to anti-complement therapy or they may develop PNH in spite of anti-complement therapy. The researchers recommended that prospective studies address these questions.

“Concerted efforts to enhance care and improve access to anti-complement therapy such as eculizumab or pegcetacoplan for patients with PNH in the ambulatory setting are needed to prevent inpatient hospitalizations with VTE and reduce associated healthcare burden and costs,” the researchers wrote in their report.

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Balfaxar is a human plasma-derived, purified, virus inactivated and nanofiltered non-activated prothrombin complex concentrate containing the coagulation factors II, VII, IX, and X and antithrombotic proteins C and S. Balfaxar temporarily corrects the coagulation defect of patients with deficiency of 1 or several of these factors.

The approval was based on data from the randomized, double-blind, LEX-209 study (ClinicalTrials.gov Identifier: NCT02740335), which evaluated the efficacy and safety of Balfaxar in patients with acquired coagulation factor deficiency due to oral VKA therapy who needed urgent surgery. Patients were randomly assigned to receive a single dose of Balfaxar (n=105) or Kcentra (n=103). Baseline International Normalized Ratio (INR) was reported to be 3.96 and 3.56 in the Balfaxar and Kcentra arms, respectively.

Results showed that treatment with Balfaxar was noninferior to Kcentra. At the prespecified interim analysis, 94.6% of patients in the Balfaxar arm met the primary endpoint achieving effective hemostasis compared with 93.5% of those in the Kcentra arm (difference, 1.1% [98% CI, -9.2%, 11.5%]; P <.001). At the final analysis, effective hemostasis was demonstrated in 94.3% of the Balfaxar group and 94.2% of the Kcentra group, resulting in a difference of 0.1% (95% CI, -8.0%, 8.2%).

The proportion of patients achieving an INR 1.5 or less at 30 minutes after the end of the infusion (secondary endpoint) was 78.1% in the Balfaxar arm vs 71.8% in the Kcentra arm (proportion difference, 6.3%; 95% CI, -5.5%, 18.0%).

The most common adverse reactions reported in Balfaxar-treated patients were procedural pain, wound complications, asthenia, anemia, dysuria, procedural vomiting, and catheter site related reaction.

Balfaxar is supplied as a lyophilized powder for reconstitution in a single-dose vial with a nominal strength of 500 Factor IX units in 20 mL reconstitution volume and 1000 Factor IX units in 40 mL reconstitution volume per vial. Dosing should be individualized based on the patient’s baseline INR value and body weight.

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Researchers sought to evaluate patients with AD in Taiwan for risk of incident VTE (deep vein thrombosis [DVT] and/or pulmonary embolism [PE]).

The researchers conducted a population-based, nationwide, retrospective, cohort study using the National Health Insurance Research Database ICD-9 and ICD-10 codes to find adults at least 20 years of age with newly diagnosed AD between 2003 and 2017 and matched (by sex and age) controls. The overall analysis included 142,429 patients in the AD cohort (mean age [SD], 44.9±18.3 years; 54.9% women) and 142,429 patients in the non-AD cohort (mean age [SD], 44.1±18.1 years; 55.9% women).  

Hazard ratios (HRs) for VTE were estimated using a Cox regression model. Sensitivity analysis and analyses stratified by sex and age were performed. Patients with records of VTE before the index date were excluded from both cohorts. The patients were followed through December 2018, death, or the occurrence of VTE (AD cohort mean follow-up, 7.15±4.4 years; non-AD cohort mean follow-up, 7.09±4.4 years). Hypertension was the most common comorbidity (17.1% AD cohort; 16.0% non-AD cohort).

A total of 1066 patients (0.75%) in the AD cohort developed VTE during follow-up (incident rate over 1000 person-years [IR], 1.05) compared with 829 patients (0.58%) in the non-AD cohort (IR, 0.82). The researchers noted a significantly increased risk for incident VTE among adults with vs without AD (HR, 1.28; 95% CI, 1.17-1.40).

An association between AD and higher risks for PE (HR, 1.30; 95% CI, 1.08-1.57; IR, 0.25) and DVT (HR, 1.26; 95% CI, 1.14-1.40; IR, 0.85) was suggested by individual analysis.

In subgroup analysis, the researchers noted an increased risk for incident VTE compared with controls by severity (mild AD HR, 1.30 and 95% CI, 1.12-1.51; severe AD HR, 1.35; 95% CI, 1.19-1.53), with no significant difference in terms of VTE risk between mild vs severe AD (HR, 1.04; 95% CI, 0.92-1.18). Similar results were reported for risks of DVT and PE.

Stratification by age showed no significance for increased risk for incident VTE associated with AD for patients younger than 45 years of age (HR, 1.03; 95% CI, 0.83-1.27), but there was a significant association for patients at least 45 years of age (HR, 1.25; 95% CI, 1.13-1.38). Stratification by sex showed a significant association for both sexes between AD and increased risk for VTE (women HR, 1.26; 95% CI, 1.11-1.43; men HR, 1.39; 95% CI, 1.22-1.59). Similar results were reported for risks for DVT and PE.

The risk for VTE remained significantly increased in patients with AD (HR, 1.45; 95% CI, 1.04-2.03) in the sensitivity analysis excluding users of systemic steroids.

Study limitations include possible unmeasured confounding, possible misclassification in ICD codes, exclusion of patients with persistent AD, and exclusion of 18- and 19-year-old patients (civil law in Taiwan defines adults as persons aged 20 years and older but many patients with AD are diagnosed at a relatively young age).

“The results of this cohort study suggest that [atopic dermatitis] in adulthood is associated with an increased risk of VTE; however, the absolute risk difference of VTE between adults with and without AD appears small,” the researchers concluded. They noted a 1.28-fold hazard for VTE among adults with AD compared with adults without AD. The researchers added, “Prompt prophylaxis with anticoagulants may be imperative in patients with symptoms that suggest VTE. This study’s findings may also have implications for interpreting pharmacovigilance studies on [Janus kinase] inhibitors.”

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There has been conflicting evidence thereafter about whether to use thromboprophylaxis in hospitalized patients, suggesting that further study is needed.

To help clarify this issue, researchers designed the randomized, phase 3 SYMPTOMS trial (ClinicalTrials.gov Identifier: NCT02379806) to determine what groups, if any, of hospitalized patients benefit from LMWH for the reduction of symptomatic VTE risk. The primary endpoint was symptomatic confirmed VTE and/or fatal or nonfatal pulmonary embolism at 30 days.

Overall, 1541 patients were enrolled and randomly assigned to receive LMWH (enoxaparin; 1278 patients) or placebo (1263 patients). In the LMWH and placebo groups, the median ages were 82 and 81 years, respectively, 40% and 40.9% of patients were male sex, and 20.3% and 22.6% of patients had been admitted to hospital because of an acute infectious disease.

Analysis suggested that patients who received LMWH did not see a reduction in the likelihood of developing a symptomatic confirmed VTE or fatal or nonfatal pulmonary embolism at 30 days (1.8% vs 2.2% with placebo; difference: 0.4; 95% CI, -1.5-0.7). Furthermore, the secondary endpoint of 30-day all-cause mortality was similar in the 2 groups (3.4% with LMWH vs 2.7% with placebo; difference: 0.7; 95% CI, -0.6-2.0).

The rates of major bleeding were also similar in the 2 groups. The study’s presenter stressed, however, that secondary findings from this trial warrant further study in this population.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.

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The investigators conducted a prospective, multicenter, interventional study of adults with persistent or chronic primary ITP and CR on TPO-RAs (ClinicalTrials.gov ID: NCT03119974).

Upon inclusion, patients underwent dose reduction and weaning of eltrombopag or romiplostim according to a standardized protocol for each TPO-RA. Eltrombopag was tapered by 25 mg every 2 weeks or stopped at week 0 for patients already at 25 mg per day. Romiplostim was tapered by 1 μg/kg every week until discontinuation. Tapering continued as long as the patient’s platelet count remained >30 × 10⁹/L.

The aim was to stop the TPO-RA by week 10. In cases of relapse (bleeding event and/or platelet count decrease <30 × 10⁹/L), the investigators increased the dosage of TPO-RA, rechallenged the patient with a TPO-RA, or initiated a new treatment line as needed.

The primary endpoint was the proportion of patients who achieved SROT (platelet count >30 × 10⁹/L and no bleeding) at week 24 with no other ITP-specific medications. Key secondary endpoints included the proportion of sustained CR off-treatment (SCROT, platelet count >100 × 10⁹/L and no bleeding), SROT at week 52, bleeding events, and response to a new course of TPO-RAs in the case of relapse.

A total of 48 patients (median age, 58.5 years; interquartile range [IQR], 41-73.5; 60.5% female) were included in the study. At TPO-RA initiation, 63% of patients had chronic ITP. The median maximal platelet count achieved on TPO-RA was 291 × 10⁹/L (range, 215 × 10⁹/L to 408 × 10⁹/L). At inclusion, most patients (83%) were on eltrombopag (17% on romiplostim). The median duration of TPO-RA exposure was 1.6 years (IQR, 1.0-3.8).

In the intention-to-treat analysis, 56.2% of patients (95% CI, 41.2-70.5) achieved SROT and 31.3% of patients (95% CI, 18.9-44.5) achieved SCROT at week 24. Similar results were observed at week 52 (SROT, 52.1%; 95% CI, 37.2-66.7; SCROT, 29.2%; 95% CI, 17.2-42.3).

Among patients who relapsed by week 24 (n=21) and week 52 (n=23), a bleeding event occurred in 57.1% and 60.9% of the patients, respectively. No severe bleeding episodes occurred. Among patients who relapsed before week 24 and were rechallenged with the same TPO-RA, 91.7% achieved CR.

“In conclusion, our study strongly supports a strategy of progressive tapering and weaning of TPO-RAs for adults with persistent or chronic ITP who achieve a stable CR on TPO-Ras,” the authors wrote in their report.

Limitations of the study included potential selection bias, possible instances of spontaneous remission, and use of eltrombopag in most patients.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures.

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In-hospital mortality ranges from 40% to 50% among patients with acute myocardial infarction (AMI) complicated by CS, which occurs in about 5% to 15% of this patient population. Investigators sought to assess procedural success and in-hospital mortality in patients with CS after AMI treated with LM PCI.

They conducted an observational study that included 2348 consecutive patients with AMI and CS treated with PCI on an intention-to-treat basis in 51 German hospitals between 2010 and 2015. Patient data were from the prospective Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte-PCI registry. The investigators performed a multivariate regression analysis for independent predictors of in-hospital mortality that included all parameters with a P value of less than 0.1 in the univariate analysis, as well as diabetes, LM PCI, triple vessel disease, sex, age, and renal insufficiency. They included all patients receiving PCI on an intention-to-treat basis. They compared continuous variables by Mann-Whitney-Wilcoxon test and significance was given to P values less than 0.05.

Patients were divided by PCI type into the following 4 groups:

• LM (n=295 [15 for protected, 280 for unprotected]; 80.1% hypertension; 70.7% hyperlipidemia; 39.6% diabetes)
• 1-vessel (n=491; 70.0% hypertension; 56.2% hyperlipidemia; 19.3% diabetes)
• 2-vessel (n=524; 78.5% hypertension; 67.9% hyperlipidemia; 30.7% diabetes)
• 3-vessel (n=1038; 80.3% hypertension; 70.0% hyperlipidemia; 40.0% diabetes)

Additional patient characteristics that varied between groups were the following:

• LM (age, 70.5±11.8 years; 26.1% women; 61.8% current smokers; 50.5% left ventricular ejection fraction [LVEF] of <40%)
• 1-vessel (age, 63.0±14.2 years; 34.0% women; 63.2% current smokers; 35.8% LVEF of <40%)
• 2-vessel (age, 67.9±12.1 years; 27.9% women; 58.4% current smokers; 40.0% LVEF of <40%)
• 3-vessel (age, 69.9±11.5 years; 29.4% women; 57.0% current smokers; 51.7% LVEF of <40%)

The investigators noted no between-group difference in the periprocedural period with antithrombotic therapy, and no differences in the use of glycoprotein IIb/IIIa, ticagrelor, clopidogrel, or aspirin. Prasugrel was used less in the LM group. There was a significant difference between the affected vessels in the initial thrombolysis in myocardial infarction (TIMI) flow grade of 0 to 1, which was less frequent in the LM group. There were no between-group differences in bleeding complications, stroke, or nonfatal MI. There was increasing extent of coronary artery disease and an increase in usage of an intra-aortic balloon pump, especially in the LM group.

The investigators found that thrombolysis in myocardial infarction 3 patency of the culprit lesion after PCI was 84.6% in the LM PCI group, 84.3% in the 1-vessel PCI group, 84.0% in the 2-vessel PCI group, and 80.8% in the 3-vessel PCI group. In-hospital mortality after PCI was 55.9% in the LM PCI group, 27.9% in the 1-vessel PCI group, 33.9% in the 2-vessel PCI group, and 46.5% in the 3-vessel PCI group. There were no between-group differences in the low bleeding rates (2.0%-2.3%).

LM PCI, TIMI flow of less than 3 after PCI, and higher age were independent predictors of mortality in multivariate analysis.

Study limitations include the lack of wide-spread availability of multiple forms of mechanical circulatory support therapies.

“…LM PCI occurs in approximately 12% of patients with CS and is associated with higher mortality in comparison to other lesion locations,” the investigators wrote. “PCI success rates are high, and these findings, therefore, support the use of PCI in patients with LM-AMI complicated by CS.”

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Knowing that patients with gastrointestinal cancer are at high risk for VTE, a team of researchers set out to compare the safety and effectiveness of DOACs in patients with GICA and VTE at a cancer center in Texas. They conducted a retrospective chart review of patients with GICA and VTE who received treatment with DOACs for at least 6 months.

The study included data from 433 patients with GICA at a single center: 300 who were prescribed apixaban and 133 who were prescribed rivaroxaban. The researchers noted that the patients received DOACs per the standard VTE dosing schedule, which included 15 mg of rivaroxaban twice daily for 3 weeks, then 20 mg daily or 10 mg of apixaban twice daily for 7 days, followed by 5 mg twice daily.

The team’s designated primary outcomes were the proportion of patients who experienced major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and recurrent VTE.  Time to bleeding and recurrent VTE were the secondary outcomes.

Their review revealed that major bleeding occurred in 3.7% (16) of the patients (95% CI, 2.1-5.9)and CRNMB occurred in 5.3% (95% CI, 3.4-7.9). Recurrent VTE occurred in 7.4% (32) of the patients (95% CI, 5.1-10.3).

They noted that the time to MB and CRNMB was longer for the patients in the apixaban cohort. Additionally, they wrote, “There was a non-significant increased risk in CRNMB in the rivaroxaban group depending on cancer type, but the sample size was small to make comparisons.” Notably, no difference existed in recurrent VTE risk between apixaban and rivaroxaban.

The researchers found that “the cumulative incidence of total bleeding, MB, CRNMB, and recurrent VTE did not significantly differ between apixaban and rivaroxaban groups.”

The researchers noted that several factors could influence the higher incidence of VTE recurrence, such as differences in the proportion of patients with GICA, metastatic disease, or higher ECOG scores.

“In conclusion, oral apixaban and rivaroxaban could be considered as anticoagulant options for the treatment of VTE in patients with GICA; however, additional multi-center clinical studies are needed to assess the clinical benefit and safety of extended treatment using DOACs in patients with GICA and VTE,” the researchers wrote in their report.

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Yan Xu, M.D., from the University of Ottawa in Canada, and colleagues examined the efficacy and safety of anticoagulants in ATE prevention among ambulatory cancer patients. The researchers performed a systematic review of studies comparing oral or parenteral anticoagulation with no anticoagulation among patients receiving systemic anticancer therapy with no other indication for anticoagulation. Data were included from 14 randomized trials involving low-molecular-weight heparins, direct oral anticoagulants, and warfarin. ATEs (myocardial infarction, ischemic stroke, intra-abdominal arterial embolism, or peripheral artery occlusion) were captured as coefficacy end points or adverse events.

The researchers observed no association for anticoagulant use with a decrease in ATEs compared with placebo or standard treatment (relative risk [RR], 0.73; 95 percent confidence interval [CI], 0.50 to 1.04). For major and minor bleeding, the RRs with anticoagulant use were 1.56 (95 percent CI, 1.12 to 2.17) and 2.25 (95 percent CI, 1.45 to 3.48). The risk of death was not reduced with anticoagulants in 13 trials that reported all-cause mortality (RR, 0.99; 95 percent CI, 0.95 to 1.02).

“Our data do not support the routine use of anticoagulation for ATE prevention in ambulatory cancer patients,” the authors write.

One author disclosed ties to the pharmaceutical industry.

Abstract/Full Text

Editorial

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Instance of VTE have been increasing. Some published evidence has related VTE risk with age, however, there remains a paucity of data overall about the relationship between age and VTE outcomes and recurrence risk.

To better evaluate these relationships, data for this study were sourced from the COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) registry, which is a multicenter cohort study conducted between 2010 and 2014 at 29 sites in Japan. For this study, patients (N=3027) with VTE were evaluated for outcomes on the basis of age. Recurrent VTE was defined as pulmonary embolism (PE) or deep vein thrombosis (DVT) symptoms with new thrombus or exacerbation of thrombus, and major bleeding was defined according to the International Society of Thrombosis and Hemostasis (ISTH) guidelines.

The patients were aged younger than 65 years (36.7%), 65 to 80 years (43.4%), or older than 80 years (19.9%). The 3 age groups comprised 55%, 62%, and 73% women (P <.001); they had a mean BMI of 24.0, 23.0, and 22.0 (P <.001); 21%, 44%, and 58% had hypertension (P <.001); and 60%, 56%, and 52% had PE with or without DVT (P =.003), respectively.

During treatment, younger patients were more likely to receive thrombolysis (P <.001), inferior vena cava filter (P =.004), and anticoagulation therapy beyond the acute phase (P =.04) compared with older patients. The youngest cohort were also more likely to discontinue anticoagulation during follow-up compared with the older cohorts (P <.001), primarily due to physician’s judgment.

At 5 years, recurrence occurred among 12.7%, 9.8%, and 7.4%; major bleeding occurred among 10.8%, 12.2%, and 14.9%; and all-cause mortality among 23.0%, 31.4%, and 38.6% of the patients aged younger than 65 years, 65 to 80 years, and older than 80 years, respectively. The cumulative incidence over time of VTE recurrence (P =.008) and mortality (P <.001), but not major bleeding (P =.37), depended on age.

Compared with the youngest group, those who were aged 65 to 80 years were at lower risk for VTE recurrence (adjusted hazard ratio [aHR], 0.71; 95% CI, 0.53-0.94; P =.02) but had higher risk for mortality (aHR, 1.20; 95% CI, 1.01-1.42; P =.03). Similarly, the patients aged older than 80 years were at lower risk for VTE recurrence (aHR, 0.59; 95% CI, 0.39-0.89; P =.01) and increased risk for mortality (aHR, 2.20; 95% CI, 1.79-2.71; P <.001) compared with the youngest cohort.

These findings may have been biased, as this is an observational study and physician’s treatment decisions, such as discontinuing anticoagulation therapy, may have influenced outcomes.

The study authors wrote, “In the current real-world VTE registry, there was no significant difference in the risk of major bleeding depending on different age groups, while younger patients showed an excess risk for recurrent VTE compared with older patients.”

Disclosures: This research was supported by Mitsubishi Tanabe Pharma Corporation. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

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Orthopedic joint procedures such as total hip arthroplasty (THA) and total knee arthroplasty (TKA) carry considerable postoperative complications, with VTE being one of the most common. Postoperative prophylaxis often consists of direct oral anticoagulants (DOAC) or low-molecular-weight heparin. With ischemic heart disease being the leading cause of death within 90 days following the procedure, researchers compared postoperative mortality rates among patients undergoing hip or knee arthroplasty receiving either aspirin or enoxaparin monotherapy.

A secondary analysis was conducted using the CRISTAL trial, a randomized crossover trial that compared aspirin with enoxaparin for VTE prophylaxis in hip or knee arthroplasty. The trial consisted of adult patients who underwent arthroplasty procedures at 31 hospitals between April 15, 2019, and December 18, 2020. Patients received daily doses of either aspirin 100 mg or enoxaparin 40 mg within 24 hours of the procedure. Treatment was administered for 35 days among patients undergoing hip arthroplasty and 14 days among those undergoing knee arthroplasty.

The primary outcome of interest was all-cause mortality within 90 days of the procedure.

A total of 23,458 patients were included in the study, of whom 14,156 received aspirin and 9302 received enoxaparin. Patient demographics were similar between both groups.

Mortality within 90 days occurred in 236 patients (1.67%) in the aspirin group and 142 patients (1.53%) in the enoxaparin group; no statistically significant difference was found between both groups (estimated difference, 0.04%; 95% CI, -0.38% to 0.46%).

A subgroup analysis for all-cause 90-day postoperative mortality based on diagnostic indication (fracture vs no fracture) revealed no significant difference between subgroups. Mortality within 90 days for a nonfracture diagnosis occurred in 0.49% and 0.41% of patients receiving enoxaparin and aspirin, respectively (estimated difference, 0.05%; 95% CI, -0.67% to 0.76%). For a fracture diagnosis, 90-day mortality was 13.1% for the aspirin group and 11.0% for the enoxaparin group (estimated difference, 1.0%; 95% CI -1.0% to 3.0%).

The causes of death within both groups were unknown, potentially limiting available information on the extent VTE prophylaxis contributes to mortality. Additionally, some patients may have received other forms of anticoagulation (DOAC, warfarin, or dual antiplatelet medications), leading to a possible confounding effect.

The study authors concluded, “[T]hese findings suggest that enoxaparin reduces the risk of symptomatic VTE without increasing the risk of mortality in comparison to aspirin after hip or knee arthroplasty.”

Disclosure: One study author declared affiliations with industry. Please see the reference for a full list of disclosures.

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A previous murine model suggested that orelabrutinib, an oral, selective, and irreversible inhibitor of Bruton’s tyrosine kinase, suppressed the activation and differentiation of B cells. Platelet counts were also increased in the model.

For this ongoing phase 2 study, researchers are assessing the safety and efficacy of orelabrutinib as a therapy among patients with persistent or chronic primary ITP. The study’s primary endpoint is the proportion of patients who reach at least 2 consecutive platelet counts of at least 50 x 10⁹/L without rescue medication within a predefined timeframe.

By the data cutoff point of February 2023, 33 patients were randomly assigned to receive orelabrutinib 50 mg (15 patients) or 30 mg (18 patients). The mean patient age was 41.9 years overall, and 63.6% of patients were female. At baseline, the mean count was 13.4 x 10⁹/L.

The median treatment time was 13.7 weeks; 12 patients in the 30 mg arm transferred to the 50 mg arm because of no primary response. Analysis showed that 36.4% of patients met the primary endpoint (22.2% in the 30 mg arm and 40% in the 50 mg arm); 2 patients reached the primary endpoint after transferring to the 50 mg arm. Nine (27.3%) patients had a durable response by the study’s predefined criteria.

Among patients who had received prior glucocorticoids or intravenous immunoglobulin, 75% in the 50 mg group reached the primary endpoint (28.6% in the 30 mg arm).

The median time to first platelet count at 50 x 10⁹/L or higher was 9 days where the initial dose was 50 mg. All treatment-related events were grade 1 or 2.

The study’s presenter noted that both doses of orelabrutinib were safe, although the 50 mg dose led to rapid responses and generally had greater efficacy, particularly among those who had received prior glucocorticoids or intravenous immunoglobulin.

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The meta-analysis is based on a literature search of relevant articles published in English on PubMed, Embase, Cinahl, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) from database inception to March 2021.

The analysis included randomized controlled trials (RCTs) that assessed use of any antithrombotic agent in patients with infectious diseases other than COVID-19. The primary outcome was all cause-mortality.

A total of 60 articles were included in the meta-analysis, but only 18 RCTs (N=16,588) were considered in the primary analysis. Of these RCTs, 7 reported on patients in the intensive care unit (ICU), and 11 assessed non-ICU patients. Sepsis was the most frequently reported syndrome (11 trials), and the median follow-up was 30 days (IQR, 28-90).

Overall, all-cause mortality was 12.7% in the treatment group and 13.2% in the control group, with a hazard ratio (HR)/relative risk (RR) of 0.96 (95% CI, 0.90-1.03; I², 0.0%).

A sensitivity analysis separately assessed RR and HR, with no changes occurring in the combined estimates. In subgroup analyses, the pooled estimate for mortality in the ICU setting was 0.98 (0.90-1.07) compared with 0.92 (0.80-1.05) in the non-ICU setting. The pooled estimate for mortality was 0.98 (0.90-1.06) for sepsis, 0.58 (0.16-2.19) for endocarditis, 0.34 (0.08-1.39) for pneumonia, and 0.87 (0.65-1.17) for other infectious diseases.

No statistically significant association was found between antithrombotic regimens and overall mortality. The pooled estimate for mortality was 1.08 (0.87-1.33) for therapeutic anticoagulant (vs no intervention or prophylactic anticoagulant), 0.94 (0.80-1.09) for prophylactic anticoagulant (vs no intervention), and 0.44 (0.24-0.81) for aspirin (vs no intervention or placebo). The pooled estimate for mortality was 0.96 (0.89-1.05) for use of other antithrombotic agent (vs no intervention, placebo, or therapeutic heparin).

Among several limitations, the RCTs available in the non-COVID-19 setting are limited with heterogenous antithrombotic treatments, and the researchers excluded COVID-19 disease. Also, secondary endpoints such as bleeding and thromboembolic events were not considered because the RCTs are inconsistent about reporting these outcomes.

“…despite the results of our meta-analysis, we believe that the role of antithrombotic treatments in acute infectious diseases needs to be further explored since evidence from RCTs is scarce and some antithrombotic agents were under-represented in clinical trials,” wrote the study authors. “Moreover, given the well-known interplay between inflammation, coagulation, and platelets aggregation it is mandatory to deeply elucidate if any antithrombotic agent could be beneficial in terms of mortality reduction.”

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Patients with an ED who are severely underweight may be given bed rest to conserve their energy, which could potentially be associated with a risk of VTE. For this reason, the researchers had a goal of characterizing features in patients with EDs who developed VTE, compared with patients who did not.

A total of 71 patients with an ED were included in this study. These patients had been admitted to Okayama University Hospital in Okayama, Japan, during a study period ranging from 2016 to 2020.

The researchers evaluated multiple patient characteristics in comparisons based on whether patients developed VTE. Predictors of VTE were identified using univariate analyses; given a small number of VTE events, multivariate statistics were not used.

In this population, 5 patients experienced VTE during hospitalization. Among patients with VTE, the median age before admission was 35 years, whereas patients without VTE had a median age of 20 years. Patients who experienced VTE were reportedly not using tobacco products or receiving hormonal contraceptive treatment.

D-dimer values were available for 35 patients of the total study population, with 15 of these patients having a level considered to be within normal limits. Among patients with elevated D-dimer levels, 13 had a mild increase, which reportedly had quickly normalized.

Univariate analysis revealed several factors present at the time of admission that appeared significantly associated with having VTE. These included the duration of the patient’s ED (P =.020), the patient’s body weight on admission (P =.022), and the patient’s body mass index on admission (P =.010). Factors present during hospitalization that appeared linked to VTE in univariate analysis included the D-dimer value (P =.022), the use of physical restraint (P =.041), and the use of a central venous catheter (P =.010). During hospitalization, median D-dimer values were 11.9 mg/L among patients with VTE and 1.0 mg/L in those without VTE.

Based on these study results, researchers concluded that in patients with an ED, possible VTE risk factors were a low body mass index, longer ED duration, and care that involved the use of physical restraints or a central venous catheter. “For the early detection of VTE, the measurement of D-dimer values and the monitoring of clinical symptoms are useful,” they wrote in their report.

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Walter Ageno, M.D., from the University of Insubria in Varese, Italy, and colleagues conducted a study involving a prospective cohort of 278 COVID-19 patients with VTE enrolled between 2020 and 2021 and a comparison cohort of 300 non-COVID-19 patients with VTE associated with hospitalization for other acute medical illnesses. Patients were followed for a minimum of 12 months after discontinuation of treatment.

The researchers found that compared with controls, patients with VTE secondary to COVID-19 more often had pulmonary embolism without deep vein thrombosis (83.1 versus 46.2 percent) and had a lower prevalence of chronic inflammatory disease (1.4 versus 16.3 percent) and VTE history (5.0 versus 19.0 percent). The two groups had a similar median duration of anticoagulant treatment (194 and 225 days) and proportion of patients who discontinued anticoagulation (78.0 and 75.0 percent). The rates of thrombotic events after discontinuation did not differ between the groups (1.5 and 2.6 per 100 patient-years).

“The low number of events seen in our study after discontinuation of therapy suggests that anticoagulant treatment for a limited period of three to six months is generally adequate for the majority of patients with COVID-19-associated venous thromboembolism,” Ageno said in a statement.

Two authors disclosed ties to the pharmaceutical industry.

Abstract/Full Text (subscription or payment may be required)

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The mainstay treatment for anterior circulation large vessel occlusion AIS is endovascular thrombectomy, which can be performed with either general anesthesia or procedural sedation. No formal guidelines have been released on which method should be preferred due to lack of evidence.

This investigator-initiated, multicenter, parallel-group, open-label, randomized clinical trial, the Anesthesia Management in Endovascular Therapy for Ischemic Stroke (AMETIS; ClinicalTrials.gov Identifier: NCT03229148), was conducted at 10 university hospitals in France in 2017 to 2020. Patients (N=273) with occlusion of the intracranial internal carotid artery and/or proximal middle cerebral artery were randomly assigned in a 1:1 ratio to receive general anesthesia (n=135) or procedural sedation (n=138) during mechanical thrombectomy.

The primary outcomes were major periprocedural complications at 7 days and functional independence at 90 days. Functional independence was defined as a modified Rankin Scale (mRS) score of 2 or fewer.

The anesthesia and sedation cohorts comprised:

• patients mean age, 72.0 (SD, 13.2) and 71.3 (SD, 14.4) years,
• 51.9% and 52.2% were women,
• 34.0% and 29.0% had a wake-up or unwitnessed AIS,
• 17.6% and 10.5% had prestroke disability,
• 63.7% and 60.9% had middle cerebral artery M1 segmental occlusion,
• the median time from angiosuite to groin puncture was 11 (IQR, 8-18) and 9 (IQR, 4-15) minutes, and
• 85.2% and 77.6% had successful reperfusion, respectively.

The composite of no major periprocedural complications and functional independence was achieved by 28.2% of the general anesthesia and 36.2% of the procedural sedation cohorts (relative risk [RR], 1.29; 95% CI, 0.91-1.82; P =.15).

Stratified by specific events, the anesthesia and sedation cohorts had similar rates of no periprocedural complications at 7 days (65.9% vs 67.4%; RR, 1.02; 95% CI, 0.86-1.21; P =.80) and functional independence at 90 days (33.3% vs 39.1%; RR, 1.18; 95% CI, 0.86-1.61; P =.32), respectively.

No significant group differences were observed for secondary outcomes of serious adverse events (RR, 0.54; 95% CI, 0.19-1.58; P =.26), progression to malignant stroke (RR, 0.53; 95% CI, 0.20-1.40; P =.19), symptomatic intracranial hemorrhage (RR, 0.93; 95% CI, 0.53-1.64; P =.81), or death at 90 days (RR, 0.90; 95% CI, 0.54-1.51; P =.69). The only exception was that general anesthesia was associated with a higher rate of hypotension than procedural sedation (87.4% vs 44.9%; RR, 0.51; 95% CI, 0.42-0.63; P <.001), respectively.

In the subgroup analysis, patients in both groups achieved the primary composite outcome at similar rates, except that procedural sedation was preferred among the subset of patients aged over 70 years (RR, 1.95; 95% CI, 1.01-3.55).

This study may have been limited, as no standard sedation protocols were included in this study.

Researchers concluded, “[O]ur trial showed that among patients with anterior circulation large-vessel occlusion acute ischemic stroke, general anesthesia and procedural sedation for mechanical thrombectomy were associated with similar rates of functional independence and major periprocedural complications.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

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“Using genetic and pharmacologic approaches coupled with clinical samples and murine models, we demonstrated a role for FXII in several vascular complications associated with SCD,” the study investigators wrote in their report.

The investigators had an aim of examining whether the coagulation factor FXII and its activated protease form (FXIIa) may be involved with thrombotic complications and vaso-occlusive crises seen in SCD. The study included 53 patients with SCD who were compared with 23 race-matched control individuals without SCD for evaluations of in vivo contact pathway activation.

Blood samples obtained from participants were used for analyses, in addition to a murine model of SCD (HbSS) that was also utilized to investigate relevant patterns in comparison with HbAA control mice.

Overall, the patients with SCD showed lower hematocrit and hemoglobin levels than control individuals did. They also had higher levels of thrombin-antithrombin complexes, D-dimer, white blood cells, and platelets than control individuals did.

In patients with SCD, markers of contact and intrinsic pathway activation were elevated relative to those of control individuals. In these patients, researchers identified higher plasma concentrations of complexes containing factors such as FXIIa, prekallikrein activator (PKa), activated factor XI (FXIa), or activated factor IX (FIXa) and their respective inhibitors (C1 esterase inhibitor [C1INH] or antithrombin [AT]), compared with control individuals. These included complexes of FXIIa:C1INH (P <.05), FXIa:C1INH (P <.01), PKa:C1INH (P <.05), and FIXa:AT (P <.05).

Plasma levels of PKa:C1INH and FIXa:AT also appeared significantly correlated with each other (P<.0001). The investigators suggested FXIIa may be involved with activation of FXI and prekallikrein in patients with SCD. Levels of FIXa:AT were also correlated with levels of FXIIa:C1INH and FX1a:C1INH in patients with SCD.

In the SCD murine model, FXIIa levels were higher than in control mice. Among other findings, in tumor necrosis factor a-challenged HbSS mice, FXII appeared to contribute to thromboinflammation, whereas tissue factor did not. FXII also appeared to be a contributor to vascular stasis and vascular congestion in HbSS mice.

Inhibition of FXII was associated with a lower degree of accumulation of fibrin and platelets in venous clots, and smaller clot volume, in both HbSS and control mice. Additionally, in HbSS mice, FXII inhibition was associated with reduced stroke severity after brain ischemia/reperfusion injury.

The study investigators noted “the unique features of SCD-related thrombosis and the evidence presented in this communication suggest that FXII(a) inhibition may be a rational and safe antithrombotic and antiadhesive strategy in SCD.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.

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Little evidence exists to guide clinicians in decisions regarding VTE prophylaxis in patients with thrombocytopenia. Researchers therefore sought to quantify the risks of bleeding and VTE associated with early VTE prophylaxis in critically ill patients with thrombocytopenia in a range of platelet counts.

The study enrolled adults admitted to an intensive care unit (ICU) on hospital day 1 who had thrombocytopenia (initial platelet count ≤150 x 10⁹/L). The participants were a subset of the Premier Healthcare Database (from 2016 to 2020).

The exposures of interest were early VTE prophylaxis on hospital day 1 and initial platelet count. The outcomes were red blood cell (RBC) transfusion on days 2 or 3 of hospital admission and a diagnosis of new VTE that was not present at admission.

A total of 137,579 patients were admitted to an ICU with a platelet count on day 1; of those, 40,009 were included in the analysis: 12,048 (30.1%) of these patients (median age, 62 years; 42% female) received VTE prophylaxis at hospital admission, and 27,961 had no VTE prophylaxis (median age, 61 years; 41% female).

The adjusted probability for early VTE prophylaxis initiation increased as the platelet count increased from 0 to 100 x 10⁹/L. At a level higher than 100 x 10⁹/L, the probability of early VTE prophylaxis was stable.

A significant interaction between platelet count and early VTE prophylaxis (P <.001) was found in the model for RBC transfusion, with the effect estimate direction indicating that the RBC transfusion risk was greater when VTE prophylaxis was initiated at a lower platelet count. In the model with natural cubic splines, the interaction between early VTE prophylaxis initiation, platelet count, and transfusion was nonlinear, with a threshold effect less than a count of 50 x10⁹/L.

No interaction was found between early VTE prophylaxis initiation and platelet count for new VTE (P =.83), including the sensitivity analysis, which used a more sensitive definition of VTE (P =.88). The risk of new VTE in patients with thrombocytopenia was low for all platelet counts.

Study limitations include the low sensitivity of the algorithm used to identify VTE and a lack of clarity in determining whether VTE prophylaxis doses decreased at lower platelet counts. In addition, minor bleeding that did not require transfusion and was undetectable could have affected clinicians’ decisions to use VTE prophylaxis.

“These results can help inform the decision to initiate VTE prophylaxis in critically ill patients with thrombocytopenia,” the study authors commented.

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ICAD is often associated with the development of a LVO, particularly among Black, Hispanic, and Asian populations. Patients who experience a LVO linked to ICAD exhibit high rates of recanalization failure following endovascular thrombectomy, often leading to the need for additional angioplasty and/or a permanent stent.

It is believed tirofiban, a selective glycoprotein IIb/IIIa receptor inhibitor, may have the ability to inhibit the bridging of fibrinogen with platelets and thus, prevent the development of arterial thrombosis in these individuals. In fact, during an endovascular thrombectomy procedure in patients who experience an ischemic stroke, tirofiban has been commonly used as an adjuvant medication.

For the study, researchers sought to explore the efficacy and safety of intravenous (IV) tirofiban prior to undergoing endovascular thrombectomy in patients with a LVO associated with ICAD. They also sought to identify any possible mediators for the clinical efficacy of tirofiban.

The prospective, randomized, double-blind, placebo-controlled Endovascular Treatment With vs Without Tirofiban for Patients with Large Vessel Occlusion Stroke (RESCUE BT) trial was conducted to evaluate IV tirofiban plus endovascular therapy vs placebo plus endovascular therapy in individuals who present with an occlusion of the internal carotid artery or middle cerebral artery within 24 hours of onset of symptoms. RESCUE-BT was performed at 55 centers in China between October 2018 and October 2021.

A total of 435 patients with acute stroke due to ICAD were included in the post-hoc analysis — 197 individuals in the tirofiban group and 238 individuals in the placebo group. The median participant age was 65 years (range, 56-72 years). Overall, 311 of the patients were men. The median National Institutes of Health Stroke Scale (NIHSS) score was 14 (range, 10-19).

Predictors of functional independence at 90 days included age, baseline NIHSS score, baseline Alberta Stroke Program Early CT [computed tomography] Score (ASPECTS), pretreatment systolic blood pressure, history of diabetes, and location of the occlusion.

A statistically significantly higher rate of functional independence at 90 days was reported in the tirofiban arm vs the placebo arm (49.7% vs 39.1%, respectively; adjusted odds ratio [aOR], 1.68; 95% CI, 1.11-2.56; P =.02). The adjusted common OR (acOR) with tirofiban vs placebo was 1.42 (95% CI, 1.10-1.99; P =.043).

Individuals in the tirofiban arm vs the placebo arm exhibited numerically lower mortality rates (1.42% vs 18.5%, respectively) and numerically higher rates of any intracranial hemorrhage (29.1% vs 23.2%, respectively), although these differences did not achieve statistical significance.

In the per-protocol population, sensitivity analysis showed that tirofiban compared with placebo was associated with a significantly higher rate of 90-day functional independence (57.6% vs 38.8%, respectively; aOR, 2.17; 95% CI, 1.31-3.60; P =.003), as well as less severity of disability (acOR, 1.82; 95% CI, 1.20-2.76; P =.005).

Additionally, the rate of first pass effect in the tirofiban arm vs the placebo arm was numerically higher (18.8% vs 13.9%, respectively; P =.17). Further, the number of thrombectomy passes was significantly lower in the tirofiban group than in the placebo group (P =.004). Thus, thrombectomy passes were examined as being a potential mediator of tirofiban effect on functional independence. Based on mediation analysis, tirofiban-reduced thrombectomy passes justified 20.0% (95% CI, 4.1%-76.0%) of the effect of tirofiban on functional independence.

“This study provides Class II evidence that tirofiban plus endovascular therapy improved 90-day outcome for patients with large vessel occlusion due to intracranial atherosclerosis,” the researchers stated.

A key limitation of the present study is that it was an exploratory analysis in an ICAD subgroup from the RESCUE BT trial and thus may have been underpowered. Further, the tirofiban dose used in this study was administered in the same fashion as in studies of patients with myocardial infarction, thus possibly resulting in a numerically higher risk for any intracranial hemorrhage.

Overall, the researchers acknowledged that tirofiban is an effective and well-tolerated adjuvant medication for endovascular thrombectomy in patients with LVO due to ICAD. However, they caution that future trials are warranted to confirm these findings.

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“The prevalence of clinically significant VTE among children with acute hematogenous MSKIs is low (2.1%); however, several easily recognized risk factors identify MSKI patients at the highest risk for VTE,” the researchers wrote in their report.

This single-center, retrospective cohort study included pediatric patients with an age between 6 months and 18 years. Patients included in the analysis were hospitalized from June 2009 through September 2018 and were diagnosed with acute osteomyelitis, septic arthritis, and/or pyomyositis. The researchers evaluated data on demographic and clinical characteristics for these patients in comparisons between those who experienced VTE and those who did not.

There were 335 patients evaluated in the study, among whom VTE was identified in 7, for a rate of 2.1%. In their analyses, the researchers found that factors including age, sex, obesity rates, and several others did not appear linked to whether or not patients experienced VTE.

However, a multivariable analysis revealed that the presence of a MRSA infection was associated with an adjusted odds ratio (OR) for developing VTE of 31.7 (95% CI, 4.7-213.5; P <.001). Additionally, intensive care unit admission or transfer were associated with an adjusted OR for VTE of 26.4 (95% CI, 3.9-180; P <.001) in multivariable analysis.

In analyses of clinical characteristics, the researchers also found various differences in clinical characteristics in patients with VTEs, compared with patients without VTEs. For example, patients with VTEs had a longer median hospital length of stay (12.8 days) than patients without VTEs did (4.7 days; P <.001).

Patients with VTEs also had longer courses of intravenous antimicrobial therapy (median 13.5 days) than were seen in those without VTEs (median 3.7 days; P =.001), and a longer time to fever resolution (median 25.7 hours, compared with 162 hours without VTE; P =.004).

“Among children with MSKIs, those with MRSA infection and those needing critical care support were most likely to develop a VTE,” the researchers stated in their report. “Providers should have a low threshold to evaluate thromboses in such patients.”

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Researchers conducted a prospective observational study in adult patients with iTTP to evaluate endothelial-mediated vasoreactivity in patients with iTTP at admission and its changes after plasma exchange therapy.

The team assessed skin microvascular blood flow and endothelium-mediated vasoreactivity using laser Doppler flowmetry and acetylcholine (Ach) iontophoresis in the forearms of patients with iTTP at admission and after plasma exchange therapy. They used data from a previously published cohort of patients with diabetes that was recorded after correction of ketoacidosis as a control group.

The study included 18 patients with confirmed iTTP (mean age, 43 years; 72% women and 28% men) and 34 control patients (mean age, 44 years; 32% women and 68% men). Among the patients with iTTP, 55% had neurological abnormalities, 50% cardiac issues, and 27.8% an acute kidney injury at admission.

At admission, patients in the iTTP group showed decreased microvascular blood flow compared with those in the control group (mean baseline perfusion index, 5.97 vs 10.1 PU; P =.03). Patients in the iTTP group also had impaired endothelial-mediated microvascular reactivity (response to Ach iontophoresis peak perfusion index, 31.9 vs 67.7 PU; P =.001) and a lower area under the curve (AUC perfusion, 9627 vs 16 475 PU; P =.03) compared with those in the control group.

Patients with iTTP underwent 2 sessions of plasma exchange therapy. The researchers report improved global microvascular blood flow (mean baseline perfusion index, 5.97 vs 11.38 PU; P =.027) and microvascular reactivity (AUC perfusion, 9627 vs 16 558 PU; P =.007) from baseline to after the first session and continued improvement in microvascular reactivity after the second session (16 558 vs 26 431 PU; P =.04).

“We showed that the microvascular reactivity of [patients with iTTP] is impaired and, therefore, could participate in organ injury besides the thrombotic process,” the researchers said in their report. “Given that patients with cardiovascular risk factors are susceptible to a lower microvascular reactivity; difference[s] between healthy [individuals] and [patients with iTTP] could be even more important than differences between [patients with diabetes] and [those with iTTP].”

Limitations of the study included the single-center design, a limited number of patients, receipt of additional treatment by nearly all patients with iTTP, use of data from patients with diabetes rather than individuals without chronic illness as the control, an inability to evaluate the endothelium of key organs with the device used in the study, and the lack of exploration of endothelium-independent vasodilation.

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Researchers conducted a retrospective cohort study to compare the risk for DVT or PE in patients with acne treated with spironolactone vs a tetracycline-class antibiotic such as doxycycline, minocycline, and sarecycline.

Data were obtained from the Truven Health MarketScan Commercial Claims database between January 1, 2017, and December 31, 2020. The database included patients from more than 160 large employers and health insurance plans in the United States.

Participants were women, had at least 1 acne diagnosis, and received a minimum of 60 days of treatment with spironolactone or a tetracycline-class antibiotic. Logistic regression was used to analyze the relationship between spironolactone use and tetracycline-class antibiotics on the probability of a PE or DVT occurring within 60 days.

A total of 33,543 participants who received spironolactone were matched with 33,543 participants who received a tetracycline-class antibiotic. The participants in both groups were a mean age of 30.9 (SD, 11.3) years, and 8.6% were currently receiving combined oral contraceptives.

Patients who were treated with spironolactone were not more likely to experience a DVT (odds ratio [OR], 0.57; 95% CI, 0.31-1.06) or PE (OR, 0.60; 95% CI, 0.26-1.37) compared with those who received tetracycline-class antibiotics.

Limitations of the study include the retrospective study design and the possibility of unmeasured confounding, although the use of matching and consideration of potential confounders, such as combined oral contraceptive use, reduced this risk.

“While there is a need to further study whether these findings generalize to other populations, this study provides reassurance that spironolactone use for acne is not associated with an increased risk for venous thromboembolism,” conclude the study authors.

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Lina Lilja, from the Sahlgrenska Academy at the University of Gothenburg in Sweden, and colleagues examined the impact of high body mass index (BMI) during childhood and puberty on the risk for adult VTE and arterial thromboembolic events (ATE) in men. Data were included for 37,672 men from the BMI Epidemiology Study Gothenburg. Information on outcomes (1,683 VTE, 144 ATE, or 1,780 any first TE event) were retrieved from national registers.

The researchers found that BMI at age 8 years and pubertal BMI change were associated with VTE, independently of each other (hazard ratio for BMI at 8 years, 1.06 per standard deviation increase; hazard ratio for pubertal BMI change, 1.11 per standard deviation increase). Compared with the normal-weight reference group, a significantly increased risk for VTE in adult life was seen for individuals with normal weight during childhood followed by young adult overweight (hazard ratio, 1.40) and individuals with overweight at both childhood and young adult age (hazard ratio, 1.48). An increased risk for ATE and TE was seen for individuals with overweight in childhood and in young adult age.

“The ongoing childhood obesity epidemic may add to the burden of adult disease through the association with thromboembolism,” the authors write.

Abstract/Full Text

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The recalled lots were distributed nationwide to wholesalers, distributors, and retailers in the US from June 2022 to October 2022:

• Dabigatran Etexilate Capsules, USP 75mg; NDC Number 67877-474-60; Lots: 22142462 (Expiration Date May 2024), 22142463 (Expiration Date May 2024), 22142464 (Expiration Date May 2024), 22143000 (Expiration Date June 2024), 22143001 (Expiration Date June 2024), 22143002 (Expiration Date June 2024)
• Dabigatran Etexilate Capsules, USP 150mg; NDC Number 67877-475-60; Lots: 22142448 (Expiration Date May 2024), 22142449 (Expiration Date May 2024), 22142450 (Expiration Date May 2024),  22143845 (Expiration Date July 2024)

The recalled products are supplied in 60-count bottles.

Dabigatran Etexilate Capsules is a direct thrombin inhibitor indicated to reduce the risk of stroke and systemic embolism in nonvalvular atrial fibrillation in adults; for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) in adults; to reduce the risk of recurrence of DVT and PE in adults who have been previously treated; and for the prophylaxis of DVT and PE in adults following hip replacement surgery.

Long-term use of a product containing a nitrosamine impurity above an acceptable level may be associated with an increased risk of cancer. To date, the Company has not received any reports of adverse events related to this recall. 

Adverse events or quality issues should be reported to the FDA’s MedWatch Adverse Event Reporting program.

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Investigators sought to evaluate clinical outcomes in patients with preprocedural TCP who received TAVR.

They conducted a systematic review and meta-analysis using EMBASE, SCOPUS, and PubMed databases to review studies reporting on preprocedural TCP and clinical outcomes in patients receiving TAVR through August 2022. Pooled outcomes were estimated with random effects models. They included 5 studies (N=142,418) of patients receiving TAVR, with a preprocedural TCP prevalence of 41.9%.

Patients with preprocedural TCP receiving TAVR had higher odds of in-hospital AKI (adjusted odds ratio [aOR], 1.81; 95% CI, 1.10-2.98; P =.019), bleeding complications (aOR, 2.69; 95% CI, 2.32-3.11; P <.01), and death (aOR, 2.72; 95% CI, 1.26-5.90; P <.01) compared with patients without preprocedural TCP receiving TAVR.

The investigators noted higher but not statistically significant odds of in-hospital acute stroke (aOR, 1.14; 95% CI, 0.94-1.37; P =.81) and vascular complications (aOR, 2.29; 95% CI, 1.87-2.81; P =.31) in patients receiving TAVR with preprocedural TCP vs patients undergoing TAVR with no TCP.

Using leave-1-out sensitivity analysis and random effects models, the investigators found similar odds ratios for in-hospital mortality. They noted overall and subgroup stability in ORs with sensitivity analysis.

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Sex chromosome aneuploidy, which involves an atypical X or Y chromosome number, is not an uncommon condition. However, it can be linked to a variety of differences, ranging from stature to biochemical variation, with possible implications for health. Prior research had suggested possible links between sex chromosome aneuploidies and VTE risk.

This study was a retrospective analysis examining X- and Y-chromosome dosage in relation to VTE incidence. Baseline and follow-up data regarding VTE diagnoses were analyzed for 108,461 unrelated individuals with records in the US Geisinger MyCode Community Health Initiative (MyCode) and for 418,725 unrelated individuals with records in the UK Biobank.

Participants with a sex chromosome aneuploidy were compared with individuals having a 46,XX or 46,XY karyotype for analyses related to VTE incidence. Because of insufficient numbers of participants from varied races and ethnicities for statistical analyses, the researchers limited their analyses to individuals who identified themselves as White.

The MyCode participants had a mean age at last visit of 58.0 years and a median follow-up duration of 15.3 (interquartile range, 9.7) years. The UK Biobank participants had a mean age at baseline interview of 56.9 years and a median follow-up duration of 12.0 (IQR, 1.6) years. Each cohort included 25 individuals who were identified as having a sex chromosome aneuploidy.

In an analysis of VTE incidence with 10-year follow-up, MyCode participants showed a rate of VTE of 1.3 events per 100 person-years among those with supernumerary sex chromosome aneuploidy, whereas the rate for participants with 2 sex chromosomes was 0.25 events per 100 person-years. The difference in these rates corresponded to a hazard ratio (HR) of 5.4 (95% CI, 3.4-8.7) in an analysis adjusted for age, sex, and ancestry.

For the UK Biobank participants, the 10-year VTE rates were 0.42 events per 100 person-years in individuals with supernumerary sex chromosome aneuploidy, compared with 0.11 events per 100 person-years in those with 2 sex chromosomes. The HR for this comparison was 4.1 (95% CI, 2.5-6.8) in an adjusted analysis.

“Adults with supernumerary sex chromosome aneuploidies compared with those having 2 sex chromosomes had a small but statistically significant increased risk of VTE,” the researchers concluded in their report. They highlighted a need for additional research to explore any clinical implications of these findings.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

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Data for this study were collected at ambulatory centers devoted to identifying and treating patients with long COVID-19 syndrome in Italy and Sweden. Patients (N=180) previously diagnosed with COVID-19 who were experiencing persistent or new-onset symptoms 12 weeks or longer after a negative COVID-19 test received a complete physical examination. The subset of patients with suspected cardiac involvement also received a complete cardiovascular examination, including echocardiography. Prevalence and risk factors associated with acute pericarditis were assessed.

The patients had a mean age of 48±16 years, 62% were women, 38% were vaccinated for COVID-19, 16% had autoimmune and allergic disorders, and 2% had coronary artery disease. The median duration of SARS-CoV-2 positivity was 21 (IQR, 14-41) days and duration of COVID-19 symptoms was 131 (IQR, 94-255) days.

At the examination, the most common symptoms were shortness of breath (52%), heart palpitations or arrhythmia (37%), and chest pain or discomfort (34%). At laboratory testing, 10% had abnormal C-reactive protein, 9% abnormal erythrocyte sedimentation rate, and 9% abnormal D-dimer.

Overall, 39 patients had acute pericarditis. The patients with acute pericarditis were mostly women (P =.0120), had autoimmune or allergic disorders (P <.0001), had longer duration of COVID-19 symptoms (P =.0106), had chest pain or discomfort (P <.0001), had heart palpitations or arrhythmias (P <.001), had abnormal C-reactive protein concentrations (P =.00101), and had abnormal erythrocyte sedimentation rate (P <.0001) compared with patients without acute pericarditis.

After a diagnosis of acute pericarditis, patients were prescribed colchicine (n=26), nonsteroidal anti-inflammatory drugs (NSAIDs; n=25), and corticosteroids (n=8). A total of 7 NSAID recipients were nonresponders and were switched to corticosteroids.

Most (n=33) patients recovered from acute pericarditis after 1 to 4 weeks of therapy.  After 1 month or more of relief from acute pericarditis symptoms, recurrence occurred among 10 patients. These recurrences were attributed to idiopathic pericarditis (n=6), COVID-19 vaccination (n=5), and/or COVID-19 recurrence (n=1).

Risk for acute pericarditis was associated with autoimmune or allergic disorders (odds ratio [OR], 4.147; 95% CI, 1.466-11.728; P =.007) and symptoms of heart palpitations or arrhythmia (OR, 3.748; 95% CI, 1.565-8.976; P =.003).

The results of this study may not be generalizable to settings that are not focused on long COVID-19 syndrome.

“Our findings suggest a high prevalence of acute pericarditis in patients with long COVID-19 syndrome,” the study authors wrote. “Autoimmune and allergic disorders, and palpitations/arrhythmias were frequently associated with pericardial disease.”

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Researchers conducted a prospective, multicenter, observational cohort study to evaluate the risk of ITP worsening during pregnancy among women with a pregestational diagnosis of ITP.

The primary outcome was the first occurrence of ITP worsening, a composite end point that included bleeding events and/or severe thrombocytopenia (<30 × 10⁹/L) or ITP treatment modification. The researchers also evaluated the recurrence of ITP worsening as well as the incidence of NITP and identified associated risk factors.

The study included a total of 348 women with ITP who were pregnant (n=180) or not pregnant (n=168). Of those, the investigators matched women by history of splenectomy, ITP status (no response, response, or complete response), and duration, yielding a group of 131 women with pregnancy (median age, 30.4 years) and a group of 131 women without pregnancy (median age, 31.4 years). They followed the groups for 15±3 months.

The team found the first occurrence of ITP worsening was not significantly different between women with ITP with or without pregnancy (53.4 vs 37.1 per 100 person-years; hazard ratio [HR], 1.35; 95% CI, 0.89-2.03; P=.16).

They observed women with pregnancy were more likely than those without pregnancy to have recurrence of severe thrombocytopenia (HR, 2.71; 95% CI, 1.41-5.23; P =.003) and treatment modification (HR, 2.01; 95% CI, 1.14-3.57; P =.017), but not recurrence of severe bleeding events (HR, 1.38; 95% CI, 0.6-2.9; P =.4).

The researchers found 14% of neonates showed NITP with a platelet count of <50 × 10⁹/L. Using multivariable analysis, they discovered NITP was associated with maternal history of a previous offspring with NITP (adjusted odds ratio [aOR], 5.55; 95% CI, 1.72-17.89; P =.004) and maternal platelet count of <50 × 10⁹/L within 3 months before delivery (aOR, 4.07; 95% CI, 1.41-11.73; P =.009).

“Our study demonstrates that the severity of ITP during pregnancy should now also be considered a risk factor. Nevertheless, women with ITP should not be discouraged if they want to become pregnant, because the prognosis for the newborn is reassuring when therapeutic measures proposed in international guidelines are observed,” concluded the researchers.

Limitations of the study included potential lack of power due to enrollment of fewer women than originally planned, use of a composite endpoint, absence of systematic testing for anti-platelet antibodies in the women with pregnancy/inability to study the

possible association between the presence of anti-platelet antibodies and risk of NITP, absence of testing antiplatelet alloantibodies in thrombocytopenic neonates, and absence of testing parental platelet phenotypes.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

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Researchers conducted a systematic review and meta-analysis after searching PubMed, EMBASE, and the Cochrane Central Register of Clinical Trials for randomized controlled trials (RCTs) through April 9, 2022, as well as ClinicalTrials.gov for any ongoing trials. Eligible RCTs included patients aged older than 18 years with thrombotic APS and reported cardiovascular outcomes in those receiving DOACs vs VKAs.

The main efficacy outcomes were a composite of arterial thrombotic events and venous thromboembolic events (VTE). The main safety outcome was major bleeding based on the definition of the International Society on Thrombosis and Hemostasis.

A total of 4 RCTs with 474 patients (234 patients assigned to DOACs and 240 patients assigned to VKAs) were included. Participants had an average age of 48.0 years, 68% were women, and their mean body mass index was 28.3. The mean percent time in the therapeutic range for patients who received VKAs was 60%, and the mean follow-up was 19 months.

Use of DOACs vs VKAs was associated with increased odds of the composite of arterial thrombotic events (10.3% vs 1.3%; odds ratio [OR], 5.43; 95% CI, 1.87-15.75; P <.001; I²=0%). The odds of having a subsequent stroke were significantly higher for participants who received DOACs compared with those who received VKAs (8.6% vs 0%; OR, 10.74; 95% CI, 2.29-50.38; P <.001; I²=0%).

The odds of VTE risk were not significantly different between participants in the DOAC group compared with those in the VKA group (1.7% vs 1.3%; OR, 1.20; 95% CI, 0.31-4.55; P =.79; I²=0%). The odds of major bleeding were not significantly different between participants who received DOACs compared with those who received VKAs (4.3% vs 4.2%; OR, 1.02; 95% CI, 0.42- 2.47; P =.97; I²=0%).

Use of DOACs was associated with increased odds of the composite outcome of arterial thrombotic events or VTE compared with use of VKAs (11.5% vs 2.5%; OR, 4.46; 95% CI, 1.12-17.84; P =.03; I²=0%). All-cause mortality was not significantly different between participants who received DOACs vs those who received VKAs (2.6% vs 1.7%; OR, 1.43; 95% CI, 0.44-4.62; P =.55, I²=0%).

In a subgroup analysis of participants with different types of thrombotic APS, those who received DOACs vs VKAs had increased odds of a composite of arterial thrombotic events and no change in the odds of subsequent VTE or major bleeding based on whether they had triple APS or another APS combination. No statistically significant subgroup effect was found in outcomes (P =.80 for arterial thrombotic events, P =.85 for VTE, and P =.45 for major bleeding).

Study limitations include the number of included studies is small and sample size is pooled. In addition, analysis is observational and rivaroxaban and apixaban were not compared with each other.

“Collectively, the findings of this study do not support the routine use of existing DOAC regimens in patients with thrombotic APS,” the investigators wrote. “Further RCTs will be required to elucidate whether higher doses of DOACs can offer convenience to patients and clinicians, while ensuring efficacy and safety.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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Some evidence suggests that patients with cancer are as much as 15 times more likely to develop VTE than are members of the general population.

Given, however, that patients with cancer may also have an increased risk of bleeding, prophylaxis is not generally recommended. Targeting prophylaxis to only those patients most likely to benefit is therefore an area of active inquiry.

Previous research has suggested that ABO blood type is predictive of VTE risk, and that blood type is linked with nearly one-third of VTE events in the general population, although the causal mechanisms are not fully understood. For this study, researchers investigated whether ABO blood type is linked with VTE risk among patients with cancer.

Overall, data from 1708 patients with cancer were included in the present analysis. The median patient age was 61 years, 46% of patients were female sex, and the most common tumor type was lung (19%). The majority (58%) of patients had intermediate-risk disease. ABO blood types included O-type (38%), A (40%), B (15%), and AB (7%).

The median follow-up was 24 months; by this point, 8.8% of patients had developed a VTE. Analysis showed that during the initial 3 months of follow-up, the time-restricted subdistribution hazard ratio (SHR) for VTE risk for non-O blood type was 1 (95% CI, 0.6-1.67), suggesting there was no association. After 3 months, however, among patients with intermediate- or low-risk thrombotic tumors, there appeared to be such an association (SHR, 1.79; 95% CI, 1.12-2.85).

This link was not present among high-risk tumor types (SHR, 0.94; 95% CI, 0.55-1.61) and was weaker after adjusting for factor VIII status.

“ABO blood type group is an easily accessible VTE predictor that can help in the clinical practice during risk assessment in patients with cancer,” the authors wrote in their report.

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The open-label, randomized controlled study compared the efficacy and safety of apixaban with warfarin for the resolution of post-MI LVT in contemporary practice. Participants were aged 18 to 80 years with a history of acute (within 1 week) or recent (within 1 month) anterior wall MI, with evident LVT on conventional transthoracic echocardiography.

The patients were assigned to apixaban (5 mg twice daily) or dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for the study duration. Clinical assessment was conducted at enrollment and at 1, 3, and 6 months.

LVT resolution at 3 months was the primary endpoint. To achieve noninferiority, apixaban had to have 95% or more LVT resolution vs warfarin.

A total of 50 patients with post-MI LVT were included and completed the follow-up, with the first patient randomized in September 2018 and the last patient completing follow-up in July 2021. Of the cohort, 25 participants received apixaban (mean age, 52±8.2 years), and 25 received warfarin (mean age, 53±7.9 years).

No patients had a stroke, transient ischemic attack or other systemic embolisms, new MI, death from any cause, unscheduled hospitalization, or clinical evidence of bleeding. At 3 months, hemoglobin level was confirmed in 20 patients (80.0%) in the apixaban group and in 19 participants (76.0%) in the warfarin group (13.3±2.6 vs 13.2±2.5 gm/dL, respectively). The warfarin group had an INR time within the time-in-therapeutic range of 73%.

Apixaban was noninferior to warfarin for LVT resolution, with no statistical difference occurring in resolution rates. At 1 month, 10 patients (40.0%) who received apixaban had LVT resolution, 13 (52.0%) had LVT regression, and 2 had persistent LVT. At 1 month in the warfarin group, 14 patients (56.0%) had LVT resolution, 10 (40.0%) had LVT regression, and 1 had persistent LVT.

At 3 months, 19 patients (76.0%) who received apixaban had LVT resolution, 5 (20.0%) had LVT regression, and 1 had persistent LVT. In the warfarin group, 20 participants (80%) had LVT resolution, and 5 (20.0%) had LVT regression. Apixaban was associated with 95% relative success in LVT resolution at 3 months vs warfarin (P <.036 for noninferiority).

At 6 months, 23 participants (92.0%) in the apixaban group and 24 (96.0%) in the warfarin group had complete LVT resolution. No patients who had the oral anticoagulant stopped after LVT resolution at 3 months had echocardiographic recurrence at 6 months.

According to multivariate adjustment analysis, an LV aneurysm (hazard ratio [HR], 1.65; 95% CI, 1.03-1.87; P <.024), a larger baseline LV thrombus area (HR, 1.63; 95% CI, 1.32-2.74; P <.031), and lower LVEF (HR, 1.39; 95% CI, 1.02-2.54; P <.043) were independent predictors of LVT persistence at 3 months.

Study limitations include the nonblinded design, small sample size, and use of echocardiography for LVT detection. Also, the findings cannot be generalized to older and sicker patients and are not powered to assess the clinical outcome.

“Our study provides additional evidence, as a small randomized controlled clinical trial, of the benefit of direct oral anticoagulants in patients with LVT after acute or recent MI,” the investigators wrote.

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The researchers conducted a retrospective cohort study to develop the new risk prediction model for VTE in the context of modern antimyeloma therapy. They included all consecutive patients diagnosed and treated at single clinic between 2008 and 2018 for the derivation cohort and all consecutive patients diagnosed and treated at an independent clinic between January 2012 and January 2020 for the external validation cohort. They extracted clinical and laboratory data from electronic medical records.

The primary outcome for this study was VTE within 1 year of treatment initiation. The team used a multivariable model to construct the risk score.

Using the derivation cohort (n=783; median age at diagnosis, 63 years; men, 55.2%; Black, 20.1%), the researchers identified significant predictors of VTE for inclusion in the model: prior VTE (subdistribution hazard ratio [sHR], 5.06; 95% CI, 1.89-13.5), prior surgery (sHR, 3.44; 95% CI, 1.96-6.02), immunomodulatory drug use (sHR, 2.17; 95% CI, 1.24-3.80), abnormal metaphase cytogenetics (sHR, 2.1; 95% CI, 1.24-3.56), and Black race (sHR, 1.71; 95% CI, 1.03-2.83).

In this cohort, the researchers reported that the risk of VTE increased significantly with increasing score, with a sHR per 1-point increase of 1.28 (95% CI, 1.19-1.39; P <.001) and a c-statistic of 0.622 (95% CI, 0.567-0.674). They found the model stratified patients into low, intermediate, and high risk, with 12-month cumulative VTE incidence of 2.7%, 10.8%, and 36.5%, respectively.

In the external validation cohort (median age, 67 years), the 12-month cumulative incidence of VTE was 11.0% (95% CI, 7.2-15.6). The team also reported that the risk of VTE increased significantly with increasing score, with a sHR per 1-point score increase in the validation cohort of 1.23 (95% CI, 1.07-1.41; P =.004) and a c-statistic of 0.587 (95% CI, 0.492-0.682).

“In conclusion, PRISM is the first validated risk prediction tool including patient-, disease-, and treatment-specific factors that was developed in the context of modern antimyeloma therapy and a patient population that is representative of demographic characteristics of the United States. However, external validation in larger data sets as well as prospective validation, which is the gold standard, will be required before routine incorporation of the PRISM score into clinical practice,” the researchers wrote in their report.

Limitations of the study included a low total number of VTE events, consideration of candidate risk factors at baseline only and not time-varying risk factors, and a lack of prospective validation of the risk prediction tool.

The post Novel Risk Prediction Tool May Identify Patients With Multiple Myeloma at a High Risk for Venous Thromboembolism appeared first on The Cardiology Advisor.

The systematic review and meta-analysis sought to summarize and assess the evidence for prespecified clinical questions associated with the perioperative management of patients who are receiving antiplatelet therapy with acetylsalicylic acid (ASA) alone, P2Y₁₂ inhibitors, or combined antiplatelet therapy to support the development of the 2022 American College of Chest Physicians (ACCP)/CHEST guidelines.

Investigators conducted a literature search in multiple databases from inception to July 16, 2020, for studies that included adult patients (aged ≥18 years) with or without coronary stents who were receiving antiplatelet therapy and required an elective procedure, a noncardiac procedure or coronary artery bypass graft (CABG), or minor procedures and who reported an outcome of interest (major and minor bleeding, arterial or venous thromboembolic events).

A total of 38 studies were included that addressed 6 patients–interventions–comparators–outcomes (PICO) questions.

In 1 randomized controlled trial (RCT) and 1 cohort study with a total of 699 patients, stopping ASA 7 days or less before the procedure, compared with stopping ASA 7 days or more, was not associated with a statistically significant difference in the risk for major bleeding, major thromboembolism, and MI, with very low certainty of evidence (COE).

Analysis of 3 RCTs and 2 cohort studies of 485 patients compared stopping ASA within 7 days before surgery to continuing ASA throughout the elective surgery. No statistically significant difference was found in the risk for major bleeding, major thromboembolism, and MI, with very low COE.

In analysis of 5 RCTs with 28,062 patients, compared with participants who received placebo perioperatively, ASA continuation was associated with an increased risk for major bleeding (relative risk [RR], 1.31; 95% CI, 1.15-1.50; high COE) and a reduced risk for major thromboembolism (RR, 0.75; 95% CI, 0.59-0.95; high COE).

A total of 1 RCT and 2 cohort studies included 638 patients with coronary stents at high or low-moderate risk for CV events who continued antiplatelet therapy perioperatively or stopped antiplatelet agents 7 to 10 days before the procedure. Continuing antiplatelet therapy perioperatively vs stopping antiplatelet therapy was not associated with a statistically significant difference in the risk for major bleeding and major thromboembolism, with low to very low COE.

Compared with no bridging during interruption in 1 cohort study with 215 patients with coronary stents who were receiving antiplatelet agents, bridging with low-molecular-weight heparin was associated with a statistically significant increased risk for major bleeding (RR, 1.86; 95% CI, 1.24-2.79) and thromboembolism (RR, 26.2; 95% CI, 1.56-441.6; very low COE).

Continuation of antiplatelet therapy compared with stopping of antiplatelet therapy was associated with a statistically significant increased risk for major bleeding in patients receiving CABG in 3 RCTs (RR, 1.68; 95% CI, 1.29-2.18), with moderate COE.

Continuing antiplatelet therapy in minor dental procedures was not associated with a statistically significant difference in major bleeding risk, compared with stopping antiplatelet therapy 7 to 10 days before the procedure, with very low COE. In addition, continuing antiplatelet therapy was not associated with a statistically significant difference in the risk for major bleeding, stroke, MI, and other major thromboembolism events in patients receiving minor ophthalmologic procedures, with low to very low COE

The researchers noted that firm conclusions were precluded by limited evidence, as a small number of high-quality studies directly evaluated the perioperative management of antiplatelet therapy. Also, certainty in the estimates of effect was low for many PICO questions and associated outcomes.

“This review highlights the urgent need for further research to address these gaps in knowledge, especially as the prevalence of patients taking 1 or more antiplatelet agents is increasing with an aging population and such patients are most likely to require a surgery/procedure,” the investigators wrote.

Disclosure: One of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

The post Strong Recommendations Lacking in Perioperative Antiplatelet Management appeared first on The Cardiology Advisor.

The investigators conducted a prospective, multicenter, observational study of patients with suspected HIT between 2018 and 2021 and hypothesized that machine-learning algorithms could be used to develop an accurate and user-friendly diagnostic tool to integrate diverse clinical and laboratory information.

The team collected detailed clinical information and laboratory data, including results from immunoassays (chemiluminescent immunoassay [CLIA], particle-gel immunoassay [PaGIA], and enzyme-linked immunosorbent assay [ELISA]) of participants. They used the washed platelet heparin-induced platelet activation assay (HIPA) as the reference standard and evaluated 5 separate machine-learning prediction models for each immunoassay.

A total of 1393 patients with suspected HIT (median age, 67.02 years; interquartile range, 57.4-75.1; 63.8% men and 36.2% women) were included in the study. Of those, 119 patients were HIPA positive and 1274 patients were HIPA negative, translating to a HIPA-diagnosed HIT prevalence of 8.5%.

To develop a practical prediction model intended for bedside use, the researchers conducted a step-wise feature selection process, balancing trade-offs between model accuracy and usability. In the feature selection process, they used a training dataset comprising 75% of the patient cohort and identified immunoassay test result, platelet nadir, unfractionated heparin use, C-reactive protein, timing of thrombocytopenia, and other causes of thrombocytopenia as predictor variables.

The researchers found the best performing models were support vector machine algorithms for CLIA and ELISA and a gradient boosting machine algorithm for PaGIA. In the validation dataset, comprising 25% of patients, they reported the area under the receiver-operating characteristic curve (AUC) of each of these models was 0.99.

The team compared numbers of false-negative and false-positive patients of these algorithms with those of the currently recommended diagnostic algorithm (4Ts score, immunoassay). They found the numbers of false-negative patients were reduced by 50% for ELISA, 66.7% for PaGIA, and 64.3% for CLIA. Also, the numbers of false-positive individuals were reduced by 29.8% for ELISA and 68.5% for PaGIA and increased by 29.0% for CLIA.

Collectively, these models underlie the novel multivariable diagnostic prediction tool, the TORADI-HIT algorithm. To facilitate its use at the bedside, the researchers made it accessible online.

“The TORADI-HIT algorithm has the potential to reduce delayed diagnosis and overtreatment in clinical practice. Future studies shall assess usability and performance in other patient populations and health care systems,” the researchers concluded in their report.

The primary limitations of the study were inclusion of mostly patients from Switzerland and use of results only from commonly employed immunoassays for model development and validation.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 

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The trial (ClinicalTrials.gov Identifier: NCT03045406) had enrolled patients with active cancer and newly diagnosed VTE, including confirmed deep-vein thrombosis (DVT) or pulmonary embolism (PE). Patients in this study were treated with either apixaban or dalteparin as monotherapy for 6 months. The study had a primary efficacy outcome of incidence of objectively confirmed VTE and a primary safety outcome of major and clinically relevant nonmajor (CRNM) bleeding, with both measured at 7, 30, and 90 days after treatment.

The study had a modified intention-to-treat population of 1155 patients, with 576 in the apixaban group and 579 in the dalteparin group. Patients reportedly showed similar demographic and clinical features and had mean ages of 67.2 years in each group.

A total of 11 recurrent VTE events were reported across the study population within the first 7 days. In the first 30 days, 35 events occurred, and by day 90, there were 63 events. Between treatment arms, in the first 7 days recurrent VTE events were reported in 1.0% of patients in the apixaban group and in 0.9% of the dalteparin group (relative risk [RR], 1.206; 95% CI, 0.370-3.930). Rates were also similar at other time points. By 90 days, these rates were 4.7% in the apixaban group and 6.2% in the dalteparin group (RR, 0.754; 95% CI, 0.464-1.225).

Rates of major and CRNM bleeding by 90 days were 8.0% in the apixaban group and 7.4% in the dalteparin group (RR, 1.075; 95% CI, 0.721-1.603). Rates of these events were also similar between the treatment groups across other time points.

In this subanalysis, patients did not show differences between apixaban and dalteparin treatment groups in rates of recurrent VTE events or bleeding events at all time points that were examined. The study investigators considered the results to support the early use of oral anticoagulation. They also noted that oral anticoagulation has benefits over subcutaneous anticoagulation in terms of ease of administration and availability for outpatient administration, potentially improving patient quality of life.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

The post Apixaban Compared With Dalteparin in Cancer-Related Venous Thromboembolism appeared first on The Cardiology Advisor.

The phase 3, multicenter, randomized, double-blinded, placebo-controlled ADVANCE trial (ClinicalTrials.gov Identifier: NCT04188379) evaluated the efficacy and safety of intravenous (IV) EFG in adults with persistent or chronic ITP.

Participants aged ≥18 years with 2 platelet counts (PLTs) of <30 × 10⁹/L at screening were randomly assigned 2:1 to receive 10 mg/kg IV of EFG or placebo for 24 weeks. The patients also had at least 2 previous ITP treatments or 1 previous and 1 concurrent treatment. Concurrent ITP therapy was allowed at a stable dose and frequency throughout.

The patients received fixed weekly dosing from weeks 1 to 4, which was followed by response-dependent weekly dosing or dosing every 2 weeks (q2w) for weeks 5 to 16, and then a fixed weekly or q2w dosing regimen from weeks 17 to 24.

The primary endpoint was the proportion of patients with chronic ITP who had a sustained PLT response (PLT of ≥50 × 10⁹/L in ≥4 of 6 visits from weeks 19 to 24 without intercurrent events such as rescue therapy at week 12 or later). Secondary endpoints included the extent of disease control in the chronic ITP group, the proportion of patients in the overall population with sustained PLT response, incidence of bleeding events, and a durable sustained platelet response in the overall population. Safety and pharmacodynamic measures also were assessed.

A total of 131 participants (118 with chronic ITP, 13 with persistent ITP) were randomly assigned for the study — 86 received EFG (mean age [SD], 46.9 [16.6] years; 54.7% female), and 45 received placebo (mean [SD] age, 51.7 [17.9] years; 53.3% female). The EFG group had a mean time since diagnosis of 10.3 (12.1) years, vs 11.1 (13.1) in the placebo group. In the EFG group, 68.6% had previous use of ≥3 ITP therapies vs 64.4% in the placebo group.

Among the patients with chronic ITP, a sustained PLT response was achieved in 21.8% (17/78) of the EFG group vs 5.0% (2/40) in the placebo group (P =.0316). All PLT-related secondary endpoints were met with EFG, including mean number of cumulative weeks of disease control (EFG 6.1 [7.66] vs placebo 1.5 [3.23]; P =.0009) and sustained platelet count response (EFG 25.6% vs placebo 6.7%; P =.0108).

Of the EFG group, 33 patients (38.4%) achieved a platelet count of 30 × 10⁹/L at week 1 compared with 5 patients (11.1%) in the placebo group. A sustained platelet count response was achieved by 90% (9/10) of patients who switched from weekly dosing to dosing every other week.

The international working group response (consecutive visits ≥7 days apart with PLTs of ≥30 × 10⁹/L and 2-fold increase from baseline in the absence of bleeding events) was observed in 51.2% (44/86) of patients who received EFG vs 20.0% (9/45) of those who received placebo.

Patients who received EFG had substantially more weeks with disease control throughout the study (10% for EFG vs 0% for placebo at weeks 20-24).

The mean immunoglobulin G levels in patients who received EFG decreased steadily during the first 4 weeks of treatment, after which the mean maximum decreases from baseline remained >60% throughout.

Treatment-emergent adverse events (TEAEs) occurred in 93.0% (80/86) of participants in the EFG group and in 95.6% (43/45) in the placebo group. The most common TEAEs were hematuria, headache, and petechiae. Serious TEAEs were reported in 8.1% (7/86) of participants in the EFG group and in 15.6% (7/45) in the placebo group, and none were treatment related.

“EFG was well tolerated and most adverse events were mild to moderate with no new safety signals,” stated the investigators in their presentation.

Disclosure: This study was funded by argenx. Please see the original reference for a full list of authors’ disclosures.

The post Efgartigimod Associated With Improved Platelet Counts in Patients With ITP appeared first on The Cardiology Advisor.

Walter Ageno, M.D., from the University of Insubria in Italy, and colleagues compared two different treatment durations of rivaroxaban in 402 adults with symptomatic isolated distal DVT in a randomized trial. Participants received standard-dose rivaroxaban for six weeks and were then randomly assigned to rivaroxaban 20 mg or placebo once daily for six weeks (200 and 202 patients, respectively). Patients were followed up for 24 months from study inclusion.

In 40 and 43 percent of patients in the additional rivaroxaban and placebo groups, respectively, isolated distal DVT was unprovoked. The researchers found that the primary efficacy outcome of recurrent venous thromboembolism during follow-up occurred in 11 and 19 percent of patients in the rivaroxaban and placebo arms, respectively (relative risk, 0.59). Recurrent isolated distal DVT occurred in 8 and 15 percent of patients in the rivaroxaban and placebo arms, respectively. Proximal DVT or pulmonary embolism occurred in 3 and 4 percent of patients, respectively. There were no major bleeding events reported.

“This benefit was mainly driven by recurrent isolated distal DVT, maintained during the 24-month follow-up, and was consistent among patient subgroups,” the authors write.

The study was partially funded by Bayer Italy. Two authors disclosed financial ties to pharmaceutical companies, including Bayer.

Abstract/Full Text (subscription or payment may be required)

The post Six Additional Weeks of Rivaroxaban Reduces Recurrent VTE appeared first on The Cardiology Advisor.

Gulsen Ozen, M.D., from the University of Nebraska Medical Center in Bellevue, and colleagues assessed MACE risk with opioids versus NSAIDs in patients with RA. The analysis included matched cohorts of 4,778 opioid-initiating and 11,218 NSAID-initiating RA patients (1998 to 2021).

The researchers found that during the study period, there were 133 MACE in the opioid-initiating group versus 392 in the NSAID group (18.2 versus 14.6 per 1,000 person-years). Similarly, all-cause deaths were higher in the opioid group (95 deaths) versus the NSAID group (228 deaths; 12.6 versus 8.2 per 1,000 person-years). While incidence rates of MACE and all-cause mortality were lower among NSAID initiators than opioid initiators, the risk for MACE was similar in propensity-matched models (hazard ratio, 1.05, 95 percent confidence interval, 0.83 to 1.32), as was all-cause mortality (hazard ratio, 1.21; 95 percent confidence interval, 0.91 to 1.62). The risk for venous thromboembolism was significantly higher in opioid initiators than NSAID initiators (hazard ratio, 2.45; 95 percent confidence interval, 1.27 to 4.74).

“We hope our findings can decrease opioid prescriptions for pain in patients with inflammatory rheumatic diseases,” Ozen said in a statement. “We have to remember that pain in inflammatory rheumatic diseases is multifactorial, and we should utilize nonpharmacological methods more often in this patient population.”

Press Release

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Researchers conducted a retrospective cohort study between March 2020 and March 2022 to assess the effects of COVID-19 vaccination status on the incidence of acute thromboembolism among adults hospitalized with COVID-19 infection. All included patients were receiving standard-dose thromboprophylaxis, and none were admitted to an intensive care unit (ICU). The primary outcome was acute thromboembolism incidence, and multiple logistic regression was used to identity associated risk factors.

A total of 1428 patients were included in the analysis, of whom 185 (13%) were vaccinated and 1243 (87%) were unvaccinated against COVID-19 infection. Of the vaccinated and unvaccinated patients, the mean age was 68.1 and 61.2 years, 53.5% and 53.5% were men, and 10.3% and 9.6% were Black, respectively. Significant differences were noted between the vaccinated vs unvaccinated groups in regard to comorbidities. These included the percentage of patients with diabetes (45.4% vs 36.0%; P =.014), heart failure (24.3% vs 7.4%; P <.0001), atrial fibrillation (16.2% vs 7.6%; P <.0001), cancer (18.4% vs 8.0%; P <.0001), chronic kidney disease (29.7% vs 16.6%; P <.0001), and immunodeficiency (14.6% vs 7.6%; P =.001).

There was an increased incidence of acute thromboembolism observed among vaccinated vs unvaccinated patients (7.0% vs 3.9%). However, after performing multiple logistic regression, this finding was not statistically significant (adjusted odds ratio [aOR], 1.35; 95% CI, 0.67-2.58; P =.38).

Further analysis between vaccinated vs unvaccinated patients showed the risk for acute thromboembolism was significantly associated with older age (68 vs 61 years; OR, 1.03; 95% CI, 1.01-1.05; P =.01) and heart failure (24% vs 7%; OR, 2.84; 95% CI, 1.35-6.00; P =.006).

In regard to the rate of mortality, no significant differences were noted between vaccinated vs unvaccinated patients (3.8% vs 4.8%; OR, 0.79; 95% CI, 0.35-1.69; P =.56).

Based on these findings, “Decisions to anticoagulate non-ICU patients hospitalized with acute COVID-19 infections may not need to consider COVID[-19] vaccination status in as part of medical decision making,” the researchers concluded.

Disclosures: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Infectious Disease Advisor.

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“Importantly, our study provides proof of the concept that targeting the Gab2-MALT1 axis using MALT1 inhibitors would be beneficial to treat thromboinflammation and thrombogenesis in DVT without inducing bleeding complications associated with direct inhibitors of coagulation,” the researchers wrote in their report.

DVT has traditionally been managed through anticoagulation, but this can enhance bleeding risk. However, evidence indicates the pathogenesis of DVT also has an inflammatory component, related to interleukin 1b (IL-1b), supporting the use of strategies aimed at inflammation.

In prior research, the group had found that Gab2, a docking protein involved in signal transduction, is a regulator in inflammatory receptor signaling and involved in activation of NF-kB and prothrombotic gene expression. In this study, they explored a mechanism by which Gab2 appears to be involved in thromboinflammation, with another protein called MALT1. MALT1 also is involved in NF-kB activation and, with CARMA1 and BCL-10 proteins, forms a system called the CBM signalosome.

The researchers investigated the roles of Gab2 through in vitro experiments using primary human umbilical vein endothelial cells, as well as in vivo experiments in mice. Techniques they used included gene silencing, using small interfering RNAs, and treatment with mepazine, an IL-1b-targeted therapy that inhibits MALT1.

After performing gene silencing, the researchers treated cells with a variety of factors, including IL-1b and others, and they measured multiple outcomes, such as P-selectin mobilization, von Willebrand factor (VWF) release, and neutrophil adhesion. Thrombus development is promoted in endothelial cells by processes like the movement of P-selectin to the exterior of cells, release of VWF, and neutrophil adhesion.

Treatment of cells in this study with IL-1b, as well as with tumor necrosis factor a, was associated with the movement of P-selectin to cell surfaces and other related outcomes. While the silencing of Gab2 did not affect P-selectin abundance, silencing of Gab2 appeared to suppress P-selectin mobilization, VWF secretion, and neutrophil adhesion to endothelial cells. Additional experiments suggested the activity of Gab2 functioned independently of factors like NF-kB and TAK1 but was associated with Rho activation.

MALT1 also diminished IL-1b-induced Rho activation, and treatment with mepazine produced results similar to what was seen with MALT1 gene silencing. MALT1 silencing also suppressed tissue factor and vascular cell adhesion molecule 1 expression.

In cells treated with Gab2 silencing, interactions of the CBM signalosome were inhibited, suggesting Gab2 has a role in assembly of this signalosome. Additionally, thrombus formation appeared to be decreased in Gab2-deficient mice, as well as in mice treated with mepazine.

The researchers concluded that Gab2 and MALT1 form an independent axis in thromboinflammation, and they noted MALT1 may be a potential target in reducing thrombosis. “Further studies are required to address the cell-specific contribution of Gab2–MALT1 signaling in the pathogenesis of DVT,” they wrote in their report.

The post Gab2 and MALT1 Influence Regulation of Thromboinflammation, Deep Vein Thrombosis appeared first on The Cardiology Advisor.

Researchers sourced data from the US Nationwide Inpatient Sample from 2000 to 2018 and used diagnosis codes to identify VTE-associated hospitalizations in patients with IBD. Additional patient and disease characteristics, such as age, sex, race, chronic steroid use, and IBD subtype were also noted.

The primary outcome was the rate of VTE-associated hospitalizations between 2000 and 2018. Secondary outcomes included risk factors for VTE-associated hospitalization, rate of VTE-associated mortality, and risk factors for mortality in patients hospitalized with a VTE.

Researchers identified 4,859,728 hospitalizations among patients with IBD — 128,236 of which were associated with a VTE. The rate of VTE-associated hospitalizations increased from 192 to 295 cases per 10,000 hospitalizations (average annual percent change [AAPC], 2.4%; 95% CI, 1.4%-3.4%; P <0.001). The increased rate remained statistically significant when stratified by Crohn disease (170-260 cases; AAPC, 2.7%; 95% CI, 1.4%-4.0%; P <.001) vs ulcerative colitis (202-259 cases; AAPC, 1.8%; 95% CI, 0.9%-2.7%; P <.001). Mortality rates among all patients hospitalized with IBD did not significantly change over time.

Independent risk factors for VTE-associated hospitalization included older age, male sex, identifying as non-Hispanic Black vs non-Hispanic White, having Clostridioides difficile or a colonoscopy during hospitalization, and a history of chronic steroid use. A multivariable analysis indicated that prior VTE or thrombophilia was associated with the highest likelihood of VTE-related hospitalization.

Study limitations include an inability to obtain more specific data regarding medications, such as biologics or VTE prophylaxis use; an inability to confirm the accuracy of outcomes and variables extracted from databases; and the cross-sectional design.

“We found that the rate of VTE increased over the past [2] decades, without significant improvement in mortality,” the study authors wrote. “As the IBD patient population is [aging], this rate may continue to increase, further [emphasizing] the need for continued education regarding the elevated risk of VTE in IBD, as well as the safety of pharmacologic prophylaxis use.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Pleases see the original reference for a full list of authors’ disclosures.

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HealthDay News — Higher levels of soluble urokinase plasminogen activator receptor (suPAR) are associated with incident venous thromboembolism (VTE) among patients hospitalized for COVID-19, regardless of D-dimer levels, according to a study published online Aug. 4 in the Journal of the American Heart Association.

Shengyuan Luo, M.B.B.S., from the Rush University Medical Center in Chicago, and colleagues used a multinational observational study of patients hospitalized with COVID-19 with suPAR and D-dimer levels measured on admission to examine whether suPAR levels identify the risk for VTE. The association between suPAR and incident VTE (defined as pulmonary embolism or deep vein thrombosis) was examined in 1,960 patients.

The researchers found that VTE occurred in 8 percent of patients and was associated with higher suPAR and D-dimer levels. A positive association was seen between suPAR and D-dimer. The odds of VTE were significantly higher comparing the third with the first suPAR tertiles after adjustment for clinical covariables, including D-dimer. When stratified by D-dimer levels and in a survival analysis accounting for death as a competing risk, the findings were consistent. A decision tree revealed that the combined cutoffs of D-dimer <1 mg/L and suPAR <11 ng/mL identified a 3.6 percent probability of VTE during COVID-19 hospitalization; this subgroup accounted for 41 percent of the total study population.

“This finding implies the possible roles of suPAR in COVID-19-related immunothrombosis,” the authors write. “suPAR may be used in conjunction with D-dimer in clinical practice for improved risk stratification of patients with COVID-19 for VTE.”

Several authors disclosed financial ties to the pharmaceutical industry; one author is named an inventor on patents related to suPAR.

Abstract/Full Text

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Among the many products comprising the booming dietary supplement industry, a growing number of individuals are turning to supplements and drinks containing caffeine and other compounds purported to increase energy. According to some reports, the energy drink market in the United States reached more than $9.7 billion in sales in 2015.¹ While many use these supplements with the aim of reducing fatigue and improving mental focus, people often seek to improve athletic performance by consuming such products.

However, experts have cautioned that, despite their popularity, caffeine-based products and other types of energy-boosting supplements could have adverse effects, especially on cardiovascular health. Because of these risks, the World Health Organization has cited consumption of energy drinks as a significant public health issue.²

While most of these risks are associated with the high levels of caffeine contained in these products, other common ingredients intended to increase energy include taurine, guarana, ginseng, glucuronolactone, and bitter orange.³ In a 2022 position statement, the European Association of Preventive Cardiology notedthat consumption of a formulation containing caffeine, taurine, and glucuronolactone “may increase arterial blood pressure, act as a platelet aggregation enhancing factor and compromise endothelial function in healthy individuals.”³

The authors point to a range of cardiovascular side effects linked to consumption of energy drinks, including coronary disease, heart failure, cardiac arrhythmias, ventricular tachycardia, and aortic dissection, among numerous other potential cardiovascular consequences.³

In addition, in a randomized, double-blind, placebo-controlled trial published in 2019, Shah et al examined the effects of 2 different energy drinks on cardiovascular parameters compared to placebo.⁴ The results showed that that consumption of the energy drinks significantly prolonged participants’ QTc interval (maximum change from baseline in Bazett’s corrected QT interval: +17.9±13.9 ms for drink A, +19.6±15.8 ms for drink B, and +11.9±11.1 ms with placebo; P =.005 for ANOVA; P =.04 and P <.01, respectively, compared to placebo).

Significant increases in peripheral and central systolic and diastolic blood pressure were also observed with the energy drinks compared to placebo (all P <.001).

These risks may be especially elevated among individuals with underlying heart conditions. A 2017 study found that the risk of cardiac arrest increased by 20% in individuals with familial long QT syndrome after drinking 2 cans of an energy drink.³

Along with the cardiovascular hazards associated with these drinks and other energy supplements in general, consuming them before exercise can further compound the risks as cardiovascular demands increase with physical activity. For example, some findings suggest that intake of 200-300 mg of caffeine 1 hour prior to aerobic exercise decreased endothelial cell function in healthy individuals, as indicated by reductions in myocardial blood flow.⁵

To gauge clinician views on the potential cardiovascular risks of consuming caffeine and other energy supplements before exercise, Cardiology Advisor checked in with Gregory M Marcus, MD, MAS, professor of medicine in residence and associate chief of cardiology for research at the University of California, San Francisco, School of Medicine, and  Jeffrey J. Hsu, MD, PhD, assistant clinical professor of medicine in the division of cardiology at the University of California, Los Angeles, School of Medicine.

What is known thus far about the cardiovascular effects of supplements such as energy drinks containing caffeine or other substances before exercising? 

Dr Marcus: The great majority of research in this area has been conducted in artificial environments using small numbers of research participants and usually examining 1 brief moment in time rather than repeated assessments.⁶ Although the data there are conflicting, there is some evidence that caffeine may help bolster athletic performance. However, these studies have generally not been designed to assess the safety of this practice nor longer-term consequences beyond mainly a single workout.

It’s important to emphasize that the possible health benefits of caffeine that have been recently highlighted in the medical literature and lay press stem from large observational studies of predominately regular coffee drinkers rather than the use of high doses of caffeine or caffeine supplements specifically before exercise.⁷

Dr Hsu: Caffeine is a common ingredient in most energy drinks, including those taken prior to exercise. While caffeine in moderate amounts – the equivalent of 2 to 4 cups of coffee – may help to improve endurance, the concern is that higher doses of caffeine may increase the risk of adverse cardiovascular effects, including arrhythmias and severe hypertension, particularly when combined with high-intensity exercise. 

Have you observed any effects related to these drinks or supplements in your own patients?

Dr Hsu: Yes, it is increasingly common for athletes – both at the recreational and elite levels – to use caffeinated “pre-workout” supplements during their training, and I have seen young athletes present with symptoms related to arrhythmias or ectopy. These often improve or completely resolve with cessation of these supplements. 

How should clinicians advise patients regarding the use of these supplements in the context of exercise?

Dr Marcus: While clinicians should, of course, encourage regular exercise, they should likely caution their patients against using supplements or energy drinks to facilitate workouts. There is no strong evidence of clinical benefit and some observational data to demonstrate harm.

These energy drinks may include other constituents, including sugar, that are overall detrimental to health. I generally recommend avoiding supplements, as the concentrations of molecules tends to exceed those in natural foods that our bodies have evolved to consume.

In general, large randomized trials of supplements tend to show either no benefit or harm to health, often with unintended adverse consequences.⁷ For example, while observational studies suggest that caffeine as can be found in commonly consumed beverages like coffee does not have a meaningful negative effect on heart rhythm disturbances and may even protect against some common heart rhythm problems, there are many case reports of young, otherwise healthy individuals experiencing clinically significant heart rhythm disturbances in the context of consuming energy drinks with high levels of caffeine.⁸

Dr Hsu: Clinicians who care for athletes should inquire about supplement use during clinic visits. Clinicians should counsel their patients that there is no “magic bullet” for optimizing their cardiovascular fitness or athletic performance, and athletes should carefully review the components of any exercise supplement they plan to consume. Those who have a history of cardiovascular disease such as arrhythmias, hypertension, or cardiomyopathy should take extra caution and review supplements with their physician prior to use. 

What are the most pressing remaining research needs regarding this topic?

Dr Marcus: Long-term investigations examining actual health-related outcomes beyond simply immediate physical performance are needed to inform clinicians and, in turn, help us to provide the most beneficial guidance to our patients.

Dr Hsu: In my opinion, with the widespread use and marketing of these exercise supplements, we need a better understanding of whether we are clearly seeing adverse cardiovascular effects in people who use these supplements. My concern is that there is little regulation of how these supplements are marketed, and combining high doses of caffeine or other stimulants with vigorous exercise may carry undue cardiovascular risk. 

References

1. Al-Shaar L, Vercammen K, Lu C, Richardson S, Tamez M, Mattei J. Health effects and public health concerns of energy drink consumption in the United States: a mini-review. Front Public Health. 2017;5:225. doi:10.3389/fpubh.2017.00225
2. Breda JJ, Whiting SH, Encarnação R, et al. Energy drink consumption in Europe: a review of the risks, adverse health effects, and policy options to respond. Front Public Health. Published online October 14, 2014. doi:10.3389/fpubh.2014.00134
3. Adami PE, Koutlianos N, Baggish A, et al. Cardiovascular effects of doping substances, commonly prescribed medications and ergogenic aids in relation to sports: a position statement of the sport cardiology and exercise nucleus of the European Association of Preventive Cardiology. Eur J Prev Cardiol. Published online January 27, 2022. doi:10.1093/eurjpc/zwab198
4. Shah SA, Szeto AH, Farewell R, et al. Impact of high volume energy drink consumption on electrocardiographic and blood pressure parameters: a randomized trial. J Am Heart Assoc. Published online May 29, 2019. doi:10.1161/JAHA.118.011318
5. Planning Committee for a Workshop on Potential Health Hazards Associated with Consumption of Caffeine in Food and Dietary Supplements; Food and Nutrition Board; Board on Health Sciences Policy; Institute of Medicine. Caffeine in food and dietary supplements: examining safety: workshop summary. Washington (DC): National Academies Press (US). 2014(5): Caffeine Effects on the Cardiovascular System. 
6. Cameron M, Camic CL, Doberstein S, Erickson JL, Jagim AR. The acute effects of a multi-ingredient pre-workout supplement on resting energy expenditure and exercise performance in recreationally active females. J Int Soc Sports Nutr. 2018;15:1. doi:10.1186/s12970-017-0206-7
7. Poole R, Kennedy OJ, Roderick P, Fallowfield JA, Hayes PC, Parkes J. Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes. BMJ. Published online November 21, 2017. doi:10.1136/bmj.j5024
8. Mandilaras G, Li P, Dalla-Pozza R, Haas NA, Oberhoffer FS. Energy drinks and their acute effects on heart rhythm and electrocardiographic time intervals in healthy children and teenagers: a randomized trial. Cells. 2022;11(3):498. doi:10.3390/cells11030498

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