ACE Inhibitors: Class & Utilization Review

Angiotensin converting enzyme inhibitors, or ACE inhibitors, are a class of medications widely prescribed for treating hypertension and other cardiac conditions. Since the approval of the first ACE inhibitors in 1981, they have contributed to the reduction in the morbidity and mortality rates of patients with chronic kidney disease, heart failure, diabetes mellitus, cardiovascular disease, and myocardial infarction (MI).¹

This article will review ACE inhibitor class and utilization and examine the mechanism by which they reduce morbidity and mortality of patients with these chronic conditions.

ACE Inhibitor Classes Review

ACE Inhibitors Mechanism of Action

ACE is part of the renin-angiotensin-aldosterone system (RAAS) and converts angiotensin I to angiotensin II. The RAAS involves the brain, kidneys, lungs, and systemic vasculature and plays a role in cardiovascular, adrenal, and renal function through blood pressure regulation and electrolyte/fluid balance.^2,3 There are three main players in the RAAS: renin, angiotensin II, and aldosterone.

In the kidneys, renin is released into the bloodstream from juxtaglomerular cells in response to a decrease in blood pressure or sodium in the distal convoluted tubule or by beta-activation.³ Renin cleaves angiotensinogen, which is produced in the liver, to angiotensin I, an inactive precursor to angiotensin II.³ ACE, found in vascular endothelium of the kidneys and lungs, is responsible for catalyzing the conversion of angiotensin I to angiotensin II.³ Angiotensin II, a potent vasoconstrictor, then binds to and activates angiotensin type I and II receptors.³

Angiotensin II causes coronary and renal vasoconstriction, stimulates sodium reabsorption, and the release of aldosterone and antidiuretic hormone.¹ Angiotensin II plays a role in cardiac remodeling by increasing left ventricular mass, as well as myocyte and vessel wall hypertrophy.¹

Aldosterone, the third major player in the RAAS, increases sodium reabsorption thereby increasing water reabsorption and potassium excretion at the distal tubule and collecting duct of nephron.³

When angiotensin II binds to angiotensin type I and II receptors in the brain, it stimulates thirst and the release of the antidiuretic hormone vasopressin that increases water reabsorption in the kidney.³ Angiotensin II also decreases the sensitivity of the baroreceptor reflex preventing it from responding appropriately when blood pressure increases.³

ACE inhibitors affect the RAAS by competitively blocking the activity of ACE. Thus, ACE inhibitors prevent the conversion of angiotensin I to angiotensin II. This decrease in angiotensin II leads to a reduction in blood pressure, aldosterone secretion, and a subsequent decrease of sodium and water retention.² Angiotensin converting enzyme inhibitors are also responsible for increasing cardiac output and index and decreasing proteinuria.¹ A decrease in the left ventricular mass has been observed when ACE inhibitors are used which help prevent cardiac remodeling.¹

In addition, angiotensin converting enzyme inhibitors contribute to an increase in bradykinin, a vasodilator, by inhibiting its degradation. As a result, bradykinin increases the levels of nitric oxide leading to vasodilation and a further decrease in blood pressure.²

ACE Inhibitors Pharmacokinetics

Angiotensin converting enzyme inhibitors are widely available in oral formulations as a single product or as combination therapy. Currently, there are ten FDA-approved ACE inhibitors on the market: benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril. Notably, enalapril is the only one with an IV formulation available. Pharmacokinetics for each ACE inhibitor varies by formulation.

In general, oral ACE inhibitors have an onset of 1 to 2 hours and lasts approximately 24 hours allowing for once daily dosing with the exception of captopril. Captopril has an onset of 15 minutes and lasts 4 to 6 hours, requiring 2 to 3 times per day dosing. Enalaprilat, the IV formulation of enalapril, has an onset of 15 minutes and lasts 6 hours.

Most angiotensin converting enzyme inhibitors are prodrugs, requiring hepatic conversion to an active metabolite. Captopril and lisinopril are not prodrugs, and thus are administered to patients with severe hepatic impairment. With the exception of fosinipril, ACE inhibitors require dose adjustment in patients with renal impairment or insufficiency.²

ACE Inhibitors Precautions & Warnings

ACE Inhibitors and Acute Kidney Injury

ACE inhibitors can cause acute renal injury, resulting in transient increases in blood urea nitrogen and serum creatinine. This increase in serum creatinine generally occurs within two weeks of starting an ACE inhibitor. Patients on diuretics, diagnosed with renal artery stenosis, or pre-existing renal impairment are at a greater risk of developing acute renal injury. As a result, in this patient population, an increase in serum creatinine is often observed immediately after starting an ACE inhibitor.^2,4 Nonetheless, renal function improves when angiotensin converting enzyme inhibition is reduced or discontinued.²

Do ACE Inhibitors Cause Hyperkalemia?

ACE inhibitors can cause hyperkalemia when used in conjunction with potassium sparing medications such as trimethoprim/sulfamethoxazole or potassium supplements, and in patients with chronic kidney disease or diabetes.⁴

Hypotension

Symptomatic hypotension leading to possible syncopal events can occur in patients that are volume depleted, hyponatremic, and on diuretics or other antihypertensive medications.^1,5 Hypotension is usually seen at initiation angiotensin converting enzyme inhibition or during dose titrations.⁵ The underlying cause should be corrected prior to restarting an ACE inhibitor.¹

Hematologic Effects

Neutropenia has been reported in patients with kidney impairment. Patients with kidney impairment and a collagen vascular disease are at a much greater risk of developing neutropenia.¹ A complete blood count (CBC) with differential test should be conducted at the beginning of treatment and periodically thereafter.⁶

ACE Inhibitors and Aortic Stenosis

Patients with aortic stenosis or hypertrophic cardiomyopathy with outflow tract obstruction can experience severe hypotension.^1,6 This is thought to be due to the reduction in afterload associated with angiotensin converting enzyme inhibitors.^1,6

ACE Inhibitors Indications

Although there isn’t enough evidence to support the use of some ACE inhibitors to treat certain conditions, they are generally used on or off labeled for the following indications:^1,6

• Heart failure
• Hypertension (adults)
• Stable coronary artery disease
• MI with left ventricular dysfunction
• ST-elevation myocardial infarction
• Proteinuria in chronic kidney disease

*Enalapril is only FDA approved for use in hypertension.

ACE Inhibitors Side Effects

ACE inhibitor-induced angioedema is a serious adverse event that occurs in 0.1 to 0.2% of patients.¹ This condition usually develops within hours to a week after starting ACE inhibitors but can also occur later during treatment course.^1,2 Black patients have a higher incidence of angioedema compared to other races, and the incidence of ACE inhibitor-induced angioedema is higher in women compared to men.²

A dry, non-productive cough is the most commonly reported adverse event that occurs in 5-20% of patients, with an onset anywhere from 1 to 6 months after the initiation of therapy.¹ If the patient can tolerate the cough, angiotensin converting enzyme inhibitors should be continued. Otherwise, switching to another ACE inhibitor is suggested.¹ Upon discontinuing the ACE inhibitor, the cough usually resolves within a few of days but can take months to fully resolve.⁵ There is a higher incidence of ACE inhibitors-induced coughing in Asian Americans.^2,4

Additional ACE inhibitors side effects that have not been previously discussed include:²

• Headache
• Pruritus
• Myalgia
• Rash
• Dizziness
• Syncope

Monitoring Parameters for ACE Inhibitors

Monitoring parameters for angiotensin converting enzyme inhibitors at the start of therapy should include:⁶

• Serum creatinine and blood urea nitrogen
• Serum electrolytes especially potassium and sodium
• CBC with differential especially in patients with collagen vascular disease
• Liver function tests
• Blood pressure
• Heart rate

Potassium and serum creatinine should be followed closely during the first month of therapy.¹ Patients with a collagen vascular disease should have CBC with differential monitored periodically throughout treatment.

ACE Inhibitors Contraindications

Patients who have a history of hereditary or idiopathic angioedema should be administered ACE inhibitors as it increases their risk of developing ACE inhibitor-induced angioedema.^2,6 Likewise, patients who had angioedema while taking ACE inhibitors or an angiotensin receptor blocker should not be rechallenged with a different ACE inhibitor.^2,6

Angiotensin converting enzyme inhibitors cause fetal harm; therefore, they are contraindicated during pregnancy.^2,6 ACE inhibitors should be discontinued once pregnancy is detected.² Caution is advised when prescribing ACE inhibitors to women of childbearing age who are not on an appropriate birth control method.

ACE inhibitors are contraindicated in patients who have received an angiotensin receptor/neprilysin inhibitor (ARNi) within the last 36 hours due to the increased risk of developing angioedema.⁷ ACE inhibitors and ARNi should not be used concurrently.

Drug Interactions

ACE inhibitors used concurrently with aliskiren in patients with diabetes should be avoided due to an increased risk of renal failure, stroke, hyperkalemia, and hypotension.²

Use caution when ACE inhibitors are used concurrently with:

• Potassium sparing medications and potassium supplements due to the increased risk of hyperkalemia
• Lithium, as the ACE inhibitor will increase serum levels of the lithium
• NSAIDs especially in volume depleted, renally impaired or elderly patients due to increased risk of acute renal failure
• Angiotensin receptor blockers, due to an increased risk of hyperkalemia and acute kidney injury

Primary ACE Inhibitors Indications

ACE Inhibitors for Hypertension: Diagnosis & Presentation

Hypertension is a major risk factor for cardiovascular disease (CVD) and accounts for more CVD deaths in the US than any other modifiable risk factor.⁴ A diagnosis of hypertension is made when the average of 2 or more seated blood pressure measurements during 2 or more office visits is greater than 140 mmHg systolic blood pressure (SBP) or 90 mmHg diastolic blood pressure (DBP).^4,8 Automated oscillometric blood pressure machines haven been shown to detect a lower blood pressure reading than manual measurement.⁸ This can lead to the misclassification of a patient’s blood pressure level. Once the average blood pressure is determined, it should be categorized into one of the following four levels to help aid in treatment decisions:⁴

• Normal: < 120 mmHg systolic blood pressure and < 80 mmHg diastolic blood pressure
• Elevated: 120-129 mmHg systolic blood pressure and < 80 mmHg diastolic blood pressure
• Stage 1: 130-139 mmHg systolic blood pressure or 80-89 mmHg diastolic blood pressure
• Stage 2: > 140 mmHg systolic blood pressure or > 90 mmHg diastolic blood pressure

Primary hypertension is a gradual increase in blood pressure due to weight gain, lifestyle factors, poor dietary habits, decreased physical activity, and/or a family history of hypertension.⁴ Patients with primary hypertension may experience headaches, vision changes, arrhythmias, chest pain, or nosebleeds; they may also be asymptomatic.

Secondary hypertension is when another medical condition causes high blood pressure. A physical exam and medical history are required to identify the potential causes. Patients with secondary hypertension may also experience the same symptoms as primary hypertension but may also present with signs or symptoms of the underlying disease causing the increase in blood pressure.⁴

Hypertension Diagnostic Workup

Diagnostic labs for primary hypertension should include fasting blood glucose, complete blood count, lipid profile, serum creatinine with eGFR, electrolytes including calcium, thyroid stimulating hormone, and urinalysis.⁴ Additional labs should be ordered to help rule out secondary causes.⁴ An electrocardiogram can be used to detect left ventricular hypertrophy and may be useful in the assessment of comorbid disease states.⁴

Hypertension Differential Diagnosis

Patients should be screened for primary and secondary causes of hypertension such as:⁴

• Obesity
• Dietary factors including excessive sodium or low potassium intake
• Renal parenchymal disease
• Renovascular disease
• Primary aldosteronism
• Obstructive sleep apnea
• Drug or alcohol induced

Hypertension Management

In patients with primary hypertension without a comorbid disease, ACE inhibitors used as monotherapy or in combination with a diuretic or calcium channel blocker are the first-line of treatment for non-black patients.^4,8 ACE inhibitors are less effective in black patients; therefore, they are second-line therapy in this population except for comorbid conditions that require the use of ACE inhibitors.^4,8 The decision to start monotherapy or combination therapy depends on how high a patient’s initial blood pressure is above the recommended target.

ACE inhibitors are considered first-line therapy in patients with hypertension and one of the following indications:^4,8

• Heart failure
• Stable ischemic heart disease
• Post stroke or transient ischemic attack
• Diabetes mellitus with nephropathy
• Chronic kidney disease regardless of race

Depending on the compelling indication, ACE inhibitors are used as either monotherapy or in combination with another medication per guideline directed treatment. ACE inhibitor doses should be titrated to the maximal beneficial dose as tolerated, or to achieve a goal blood pressure based on compelling indication.

ACE Inhibitors in Heart Failure: Diagnosis & Presentation

Heart failure is a clinical syndrome in which the heart is not capable of pumping enough blood to sustain bodily functions due to impaired ventricular function.^7,9 Patients experiencing heart failure typically present with signs or symptoms of volume overload or reduced cardiac output such as peripheral edema, pulmonary rales, recent weight gain, paroxysmal nocturnal dyspnea, exercise intolerance, abdominal swelling, and fatigue.⁹ Dyspnea on exertion is the most commonly observed symptom.⁷

A clinical diagnosis of heart failure is made based on history, physical examination, laboratory tests, and imaging.⁹ During the physical exam, the degree of a patient’s clinical congestion should be assessed. The degree of congestion can guide initial treatments and titrations as well as help determine prognosis.⁷

The Framingham diagnostic criteria for heart failure looks for the absence or presence of key components associated with heart failure during the initial evaluation.⁹ Studies have demonstrated these criteria to be highly sensitivity (97%) at detecting systolic heart failure; therefore, it is widely accepted as a tool for aiding in the diagnosis of heart failure.⁹ When the Framingham diagnostic criteria are not met, heart failure in general, and diastolic heart failure can be ruled out.⁹

After a diagnosis of heart failure is made, patients should be classified into one of the four categories based off their left ventricular ejection fraction (LVEF):⁷

• Heart failure with reduced ejection fraction (HFrEF): LVEF < 40%
• Heart failure with improved ejection fraction (HFimpEF): previous LVEF < 40% with a follow up measurement of LVEF > 40%
• Heart failure with mildly reduced ejection fraction (HFmrEF): LVEF 40-49%
• Heart failure with preserved ejection fraction (HFpEF): LVEF > 50%

It is important to classify patients as the prognosis, initial treatment, and response to treatment differs for each classification.⁷

Heart Failure Diagnostic Workup

Diagnostic information aids in the clinical diagnosis of heart failure. Initial lab tests should include B-type natriuretic peptide, CBC, liver and renal function, serum electrolytes including calcium and magnesium, iron studies, fasting lipid panel, glucose, thyroid stimulating hormone level, and urinalysis.^7,9 A B-type natriuretic peptide level is proven to be a more reliable test than N-terminal pro-BNP, especially in older populations, and have a high negative predictive value (therefore effectively ruling out heart failure if normal).⁹ However, obesity decreases the levels of BNP and NT-proBNP, thus reducing the diagnostic sensitivity in this population.⁷

A chest x-ray can be used to identify pulmonary congestion as well as to reveal alternative causes or sources of observed symptoms.⁷ A diagnosis of heart failure is more likely in the presence of pulmonary venous congestion and interstitial edema; however, it cannot be used as the only diagnostic factor.⁹ Electrocardiography helps to identify other cardiac causes that may require further workup.⁹

An echocardiogram confirms the diagnosis of systolic heart failure, and identifies the degree of dysfunction. Although an echocardiogram can assist with the diagnosis of diastolic heart failure it is not very sensitive. Echocardiography findings that support a diagnosis of diastolic heart failure include elevated left atrial pressure, impaired left ventricular relaxation, and decreased compliance.⁷ It is not uncommon to make a diagnosis of diastolic heart failure without a conclusive echocardiogram.⁹

Heart Failure Differential Diagnosis

In addition to coronary artery disease, the number one cause of heart failure, patients should be screened for:^7,9

• Hypertension
• Cardiomyopathy: idiopathic (most common type), postpartum, hypertrophic, toxic (alcohol, cocaine), restrictive
• Valvular heart disease
• Endocrine/metabolic disorders
• Infections causing myocarditis, pericarditis
• Arrhythmia
• Collagen vascular disease
• Cardiotoxicity from chemotherapy such as anthracyclines

Heart Failure Management

ACE inhibitors reduce morbidity and mortality in HFrEF thereby are first-line therapy in patient when an ARNi can’t be used.⁷ Patients that have HFrEF and hypertension should be started on ACE inhibitors and beta blockers.^4,8 Doses should be started low and titrated up to the target dose of the particular ACE inhibitor as tolerated.⁷ Patients who are asymptomatic may benefit from treatment with an ACE inhibitor.¹

Patients who have diabetes and symptomatic HFrEF benefit from ACE inhibitors in combination with a beta blocker to reduce risk of heart failure, hospitalization, and death.¹⁰ Caution should be taken in prescribing beta blockers to those with diabetes due to their decreased sensitivity to hypoglycemic symptoms.

ACE inhibitors decrease mortality and can prevent HFrEF.⁷ Therefore, there may be some benefit in starting an ACE inhibitor in patients with current or previous HFmrEF as a third line treatment option if the potential benefits outweigh the risks.⁷ Along the same lines, patients who are considered to have pre-heart failure with LVEF < 40% should be started on an ACE inhibitors to help prevent symptomatic heart failure from developing and reduce mortality.⁷

Chronic Kidney Disease Diagnosis & Presentation

Chronic kidney disease (CKD) is defined as having an abnormality in either the kidney structure or function for greater than 3 months.¹¹ Patients must have one or more of the following to meet the definition:¹¹

• GFR < 60 mL/min/1.73m2
• Albuminuria
• Urine sediment, histology or imaging suggestive of kidney damage
• Renal tubular disorder
• History of kidney transplant

Patients may present with gross hematuria complaints of foamy urine, nocturia, flank pain or decreased urine output; however, the majority of cases are identified through routine serum chemistry and urine studies.¹¹ Patients with advanced CKD can have changes in their mental status, fatigue, nausea, metallic taste, unintentional weight loss, peripheral edema, pruritus, vomiting, or dyspnea.¹¹

A detailed physical exam and history can help identify underlying causes of CKD as well as determine a timeline to distinguish chronic from acute kidney injury.¹¹ If it is determined that the abnormality in the kidney function or structure is less than 3 months, then it is acute kidney injury which is treated differently. A patient’s volume status should be assessed during the initial evaluation to help guide treatment.¹¹

CKD Diagnostic Workup

Diagnostic labs include renal function, lipid panel, serum bicarbonate, electrolytes including calcium and phosphate, parathyroid hormone, vitamin D, iron and urine levels. A kidney ultrasound can help detect urinary obstruction.¹¹

CKD Differential Diagnosis

It is important to determine if there are underlying causes of CKD as this can help with treatment decisions. Common causes of CKD are:

• Urinary obstruction
• Medication toxicity
• Exposure to nephrotoxins in the environment
• Chronic infection
• Diabetes
• Hypertension
• Malignancy
• Autoimmune disease

CKD Management

In addition to the cardio- and renoprotective benefits that ACE inhibitors have, they also slow kidney disease progression.⁵ Therefore, ACE inhibitors are first-line therapy in patients with CKD with albuminuria, with or without hypertension or diabetes.^5,11

ACE Inhibitors and Diabetes: Diagnosis & Presentation

Polyuria, polydipsia, polyphagia, blurry vision, poor wound healing, fatigue, numbness, and tingling are the main signs and symptoms associated with diabetes; however, not all patients present with symptoms.¹² Asymptomatic patients with two or more risk factors for developing diabetes should be screened annually.¹² Risk factors include, but are not limited to:¹²

• Overweight or obesity
• Sedentary lifestyle
• Family history of diabetes
• Presence of CVD
• Medication exposure, including to antipsychotics, chronic glucocorticoids
• Hypertension

A diagnosis of diabetes can be made when patients have classic symptoms of hyperglycemia or hyperglycemic crisis with random glucose of > 200 mg/dL or when one or more of the following criteria are met on two separate occasions:^12,13

• Fasting blood glucose > 126 mg/dL
• 2 hour plasma glucose > 200 mg/dL during an oral glucose tolerance test with a 75 g oral glucose tolerance test
• Hemoglobin A1c (HbA1c) > 6.5%

The HbA1c can be falsely low or elevated in certain conditions. For instance, chronic liver disease, and acute blood loss can falsely lower the HbA1c while hypertriglyceridemia, iron deficiency anemia, and splenectomy falsely elevate it.¹²

Diabetes Diagnostic Workup

Fasting plasma glucose or 2 hour plasma glucose tolerance test (for pregnant patients) and HbA1c tests are the gold standard for diagnosing diabetes.¹³ Fasting plasma glucose must be obtained from a venous blood draw, as glucometer or continuous glucose monitoring measurements should not be used for diagnosis.¹² Likewise, HbA1c should also be measured from a venous blood sample.¹² It is important that HbA1c tests are conducted in a National Glycohemoglobin Standardization Program (NGSP) certified laboratory and is consistent with the Diabetes Control and Complications Trial (DCCT) reference assay.^10,12

Diabetes Management

ACE inhibitors decrease the risk of cardiovascular events and offer renal protection in patients with diabetes. Because of this, they are first-line therapy in patients that have diabetes and one of the following compelling indications: heart failure, hypertension without albuminuria, hypertension with presence of microalbuminuria, albuminuria, proteinuria, or LV hypertrophy, CKD or coronary artery disease.^4,10,11

Depending on the compelling indication, ACE inhibitors are used as either monotherapy or in combination with another medication per guideline directed treatment. ACE inhibitor doses should be titrated to the maximal beneficial dose tolerated. ACE inhibitors can also decrease the onset of new diabetes in patients with an impaired fasting blood glucose or glucose tolerance test.¹⁰

ACE Inhibitors Post MI Management

ACE inhibitors reduce the incidence of both nonfatal and fatal major cardiovascular events in patients that have suffered an ST elevation MI (STEMI). ACE inhibitors should be initiated in all patients with STEMI of anterior location, heart failure or LVEF < 40% unless there are known contraindications. The greatest benefit was seen when ACE inhibitors were started within the first 24 hours of the MI.¹⁴

Patients can develop severe heart failure post STEMI; therefore, ACE inhibitors should be administered provided there are no contraindications. It is reasonable to give ACE inhibitors to all patients post STEMI unless contraindicated.

Narrow ACE Inhibitors Indications

ACE Inhibitors and Migraines

Lisinopril and enalapril have been shown to decrease the frequency and severity of migraine attacks. Thus, ACE inhibitors can be used for prophylactic management of migraines in patients that do not respond to or have a contraindication to conventional therapies.¹⁵

Scleroderma

ACE inhibitors are first-line therapy for patients in scleroderma renal crisis which is characterized by a sudden onset of severe hypertension. A calcium channel blocker can be added as a second line agent when blood pressure is not adequately controlled with ACE inhibitors alone.¹⁶

Glomerular Disease

Proteinuria, hypertension, and edema are common complications associated with glomerular disease. ACE inhibitors can reduce proteinuria up to 50% in a dose dependent manner. This makes them a favorable option in glomerular disease, especially when hypertension is also present.¹⁷

Nephrotic Syndrome with Proteinuria

ACE inhibitors reduce proteinuria by up to 50% and are considered first-line therapy for nephrotic syndrome when proteinuria is present. A reduction in proteinuria decreases the risk of thromboembolic and metabolic complications, and infection risk can contribute to the development of nephrotic syndrome.¹⁷

Summary

Angiotensin converting enzyme inhibitors are used for a variety of indications and have been shown to reduce morbidity and mortality through cardio and renoprotective benefits. ACE inhibitors should be used according to guidelines in patients with no known contraindications to their use.

References

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3. Fountain JH, Lappin SL. Physiology, Renin Angiotensin System. StatPearls. NCBI Bookshelf version. StatPearls Publishing; 2022. Accessed October 7, 2022.

4. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71e127-248. doi:10.1016/j.jacc.2017.11.006

5. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int.2021;99(3S):S1-S87. doi:10.1016/j.kint.2020.11.003

6. Goyal A, Cusick AS, Thielemier B. ACE Inhibitors. StatPearls. NCBI Bookshelf version. StatPearls Publishing; 2022. Accessed October 7, 2022.

7. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guidelines for management of heart failure:a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145:e895-1032. doi:10.1161/CIR.0000000000001063

8. Ferdinand, KC, Nasser SA. Management of Essential Hypertension. Cardiol Clin. 2017;35:231-246. doi:10.1016/j.ccl.2016.12.005

9. King M, Kingery J, Casey B. Diagnosis and evaluation of heart failure. Am Fam Physician. 2012;85(12);1162-1168.

10. Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020;41:2330-2323. doi:10.1093/eurheartj/ehz486

11. Chen TK, Knicely DH, Grams ME. Chronic Kidney Disease Diagnosis and Management A Review. JAMA. 2019;322(13):1294-1304. doi:10.1001/jama.2019.14745

12. Pippitt K, Li M, Gurgle HE. Diabetes Mellitus: Screening and Diagnosis. Am Fam Physician. 2016:93(2):103-109.

13. American Diabetes Association. Classification and diagnosis of Diabetes: Standards of Medical care in Diabetes – 2019. Diabetes Care. 2019;42(S1):S13-S28.

14. O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA Guideline for Management of ST Elevation Myocardial Infarction. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127:e362-e425.doi:10.1161/CIR.0b013e3182742cf6

15. Nandha Rm Singh H. Renin angiotensin system: a novel target for migraine prophylaxis. Indian J Pharmacol. 2012;44(2):157-160. doi:10.4103/0253-7613.93840

16. Fernandez-Codina A, Walker KM, Pope JE. Treatment Algorithms for Systemic Sclerosis According to Experts. Arthritis Rheumatol. 2018;70(11):1820-1828. doi:10.1002/art.40560C

17. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Internal. 2021;100(45):S2-S276. doi:10.1016/j.kint.2021.05.021

Author Bio

Emilie White, PharmD is a residency trained clinical pharmacist and medical writer. She has provided direct patient care to hospitalized patients for over a decade. Her clinical practice areas of interest include critical care, infectious diseases, and autoimmune disorders.