Early Lipid-Lowering Therapy May Reduce Risk for Recurrent Cardiovascular Events

Risk for recurrent cardiovascular (CV) events among patients with a recent acute coronary syndrome (ACS) hospitalization may be reduced with early intensification of lipid-lowering therapy posthospitalization, according to a study presented at the National Lipid Association (NLA) Scientific Sessions 2023, held in Atlanta, Georgia, between June 1 and June 4, 2023.

The ongoing VICTORION-INCEPTION trial (ClinicalTrials.gov Identifier: NCT04873934) is planned to be completed in 2024. It is a phase 3b, randomized, parallel-group, open-label study that includes 384 patients aged at least 18 years from more than 60 locations across the United States.

Researchers aim to examine the effect of inclisiran added to usual care vs usual care alone on low-density lipoprotein cholesterol (LDL-C) concentrations among patients recently hospitalized for ACS who have LDL-C concentrations equal to at least 70 mg/dL despite statin therapy. Percentage change from baseline to Day 330 in LDL-C concentration and proportion of patients at Day 330 achieving LDL-C of less than 70 mg/dL are the primary endpoints.

Secondary outcomes of the study will be changes in intensity of lipid-lowering therapy from baseline to Day 330, the proportion of patients discontinuing statins at Day 330, the proportion of patients achieving prespecified LDL-C targets after Day 90 and Day 330, and absolute changes from baseline to Day 330 in LDL-C.

Inclusion criteria include ACS within 5 weeks (inpatient/outpatient) of enrollment and LDL-C concentration of at least 70 mg/dL or non-high-density lipoprotein cholesterol of at least 100 mg/dL despite statin therapy. Additionally, patients will have fasting triglyceride concentrations of less than 4.52 mmol/L at screening and estimated glomerular filtration rate of greater than 20 mL/min.

Patients will be randomly assigned in a 1:1 ratio to inclisiran plus usual care (n=192) or usual care alone (n=192). Inclisiran therapy will be inclisiran sodium 300 mg subcutaneously twice yearly after initial doses at baseline and 3 months. The researchers plan to discontinue inclisiran in patients with unexplained creatinine kinase values, changes in liver parameters meeting study drug interruption criteria, or with intolerable adverse events. Statin therapy and usual care will continue among patients in both groups.

The researchers noted that usual care may include anti-PCSK9 monoclonal antibodies in the usual care group only, or inclisiran in the usual care group if the treating physician prescribes it (acquired through commercial outlet). The discretion of the treating physician will be used for adjustments in therapy during the study other than for inclisiran in the inclisiran arm. LDL-C values obtained as part of the study will not be accessible by treating physicians, however at their discretion, physicians can perform these assessments.

Study limitations include patients in the usual care only arm receiving inclisiran by treating physicians.

Disclosure: This research is supported by Novartis Pharmaceuticals Corporation. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.