All angiotensin-converting enzyme (ACE) inhibitors are approved by the Food and Drug Administration to treat hypertension.1-11 Captopril is approved to treat diabetic nephropathy.10 Captopril, enalapril, fosinopril, lisinopril, and quinapril are approved to treat heart failure (HF).3,8-11 Ramipril and trandolapril are approved to treat symptomatic HF in stable patients within the first few days following myocardial infarction.2,6 Captopril and trandolapril are approved to treat left ventricular dysfunction following myocardial infarction (MI) and enalapril is approved for asymptomatic left ventricular dysfunction.2,8,10 Lisinopril is approved to reduce the signs and symptoms of HF in people who are not responding adequately to diuretics and digitalis.1 Lisinopril is approved to reduce mortality in treatment of stable patients within 24 hours of acute MI.1 Ramipril is approved to reduce the risk of MI, stroke, or death from cardiovascular causes in patients 55 years or older at high risk of developing a major cardiovascular event due to history of coronary artery disease, stroke, peripheral vascular disease, or diabetes that is accompanied by at least one other cardiovascular risk factor (hypertension, elevated total cholesterol levels, low HDL levels, cigarette smoking, or documented microalbuminuria).6 Perindopril is approved for patients with coronary artery disease to reduce the risk of cardiovascular mortality and nonfatal MI.5
Hypertension
ACEIs are listed in national and international guidelines as one of several classes of antihypertensive medications for the first-line management of hypertension.12-15 In the 2017 hypertension guidelines from the American College of Cardiology and American Heart Association (ACC/AHA), ACE inhibitors are listed along with calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs), or thiazide-type diuretics as initial antihypertensive treatments in the general non-black population [Strong Recommendation (Level A-SR)]15
A 2016 meta-analysis was done of placebo-controlled trials (a meta-regression analysis restricted these trials after 2000), active controlled trials, and head-to-head randomized trials comparing two first-line antihypertensive monotherapies, ACE inhibitors and ARBs, in patients without HF.16 This analysis looked at 106 randomized trials with 254 301 patients. It found that each significantly reduce the outcomes of all-cause mortality, cardiovascular death, and MI and there was no difference in outcomes between these drugs.
Heart Disease
The renin-angiotensin-aldosterone system is a key component in the development of cardiovascular disease and high blood pressure.14,17,18 Heart failure management guidelines recommend the inhibition of angiotensin by an ACE inhibitor or ARB as a key component of the treatment plan for people with hypertension and heart failure with reduced ejection fraction (HFrEF).14,18,19 Studies have shown ACE inhibitors may reduce HF hospitalizations and death in people with HFrEF.20-24
The 2017 ACC/AHA hypertension guidelines recommend:15
- Adults with stable ischemic heart disease and hypertension (BP ≥ 130/80 mm Hg) use ACE inhibitors, ARBs, or beta blockers as first-line pharmacological therapy [Strong recommendation (Level B-R)].15
- Adults with HFrEF and hypertension should be prescribed ACE inhibitors, ARBs, or beta blockers titrated to attain a BP of less than 130/80 mm Hg [Strong recommendation (Level C-EO)].15
- Adults with heart failure with preserved ejection fraction and persistent hypertension after management of volume overload should be prescribed ACE inhibitors, ARBs, or beta blockers titrated to attain a systolic BP of less than 130 mm Hg [Strong recommendation (Level C-LD)].15
A 1993 multicenter randomized clinical trial of 19 394 patients assessed the efficacy of lisinopril, transdermal glyceryl trinitrate, and their combination on ventricular function and survival for 6 weeks following an acute MI.25 The study found that lisinopril started within 24 hours of the acute MI significantly reduced overall mortality (odds ratio [OR] 0.88, 95% confidence interval [CI] [0.79 – 0.99]) and the combined outcome measure of mortality and severe ventricular dysfunction (OR 0.90, 95% CI [0.84 – 0.98]).
A 1993 double-blind randomized controlled trial of enalapril on 108 patients with left ventricular ejection fraction ≤0.35 but without clinical heart failure found that enalapril slows or reverses left ventricular dilatation in asymptomatic patients.26 Radionuclide end-diastolic volume decreased in enalapril patients (120 ± 25 to 113 ± 25 mL/m2, mean ± SD) increased in placebo patients (119 ± 28 to 124 ± 33 mL/m2).
Kidney Disease
Studies have shown the progression of kidney disease may be slowed by ACE inhibitors.27 The Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) recommends that an ACE inhibitor or ARB be used in both diabetic and non-diabetic adults with CKD and urine albumin excretion >300 mg/24 hours.28 The guideline also suggests an ACE inhibitor or ARB be used in diabetic adults with CKD and urine albumin excretion 30 to 300 mg/24 hours.
The 2017 ACC/AHA Hypertension Guidelines say that ACE inhibitors are a reasonable antihypertensive treatment for adults with CKD to slow kidney disease progression [Moderate recommendation (Level B-R)].15 The previous (JNC8) guideline also recommends that adults with CKD should include an ACE inhibitor or an ARB as part of their antihypertensive treatment to improve kidney outcomes. [Moderate recommendation (Grade B)]12
A 2015 network meta-analysis of randomized trials examined the effect of antihypertensives on all-cause mortality and end-stage renal disease in adults with diabetic kidney disease.27 It found ACEI monotherapy significantly reduced progression to end-stage renal disease in people with diabetes compared to placebo (OR 0.71, 95% CI [0.51 – 1.01]). Combination therapy with ARB and ACEI was superior (OR 0.62, 95% CI [0.43 – 0.90]), but this combination has some risk of increased hyperkalemia and acute kidney injury.
A prospective randomized, double-blind, placebo-controlled trial of captopril on 147 normotensive patients with type 1 diabetes with persistent albumin excretion 20 to 200 mcg/min over 24 months found that 6.0% (4/67) of patients on captopril and 18.6% (13/70) of patients on placebo progressed to clinical proteinuria.29 The albumin excretion rate decreased annually by 17.9% (95% CI [-29.6% – -4.3%]) for people taking captopril, while it increased 11.8% (95% CI [-3.3% – 29.1%]) in the placebo group (p=0.004).
References
- Prinivil [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2016.
- Trandolapril [package insert]. Laurelton, NY: Epic Pharma, LLC; 2017.
- Fosinopril sodium [package insert]. Miami, FL: Ciplo USA Inc; 2015.
- Moexipril hydrochloride [package insert]. Teva Pharmaceuticals USA Inc; 2016.
- Aceon [package insert]. North Chicago, IL: Abbot Laboratories; 2011.
- Altace [package insert]. New York, NY: Pfizer Laboratories; 2017.
- Lotensin [package insert]. Parsippany, NJ: Validus Pharmaceuticals LLC; 2014.
- Vasotec [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; 2015.
- Zestril [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2014.
- Capoten [package insert]. Spring Valley, NY: Par Pharmaceutical Companies, Inc.; 2012.
- Accupril [package insert]. New York, NY: Parke Davis, Pfizer; 2017.
- James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults. JAMA 2014; 311 (5): 507-520.
- Qaseem A, Wilt TJ, Rich R, Humphrey LL, Frost J, Forciea MA. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med 2017; 166 (6): 430-430.
- Rosendorff C, Lackland DT, Allison M, et al. Treatment of hypertension in patients with coronary artery disease: a scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. Circulation 2015; 131 (19): e435-470.
- 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: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2017.
- Bangalore S, Fakheri R, Toklu B, Ogedegbe G, Weintraub H, Messerli FH. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients without heart failure? Insights from 254,301 patients from randomized trials. Mayo Clin Proc 2016; 91 (1): 51-60.
- Unger T. The role of the renin-angiotensin system in the development of cardiovascular disease. Am J Cardiol 2002; 89 (2a): 3A-9A; discussion 10A.
- Yancy CW, Jessup M, Bozkurt B, et al. 2016 ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure: an update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol 2016; 68 (13): 1476-1488.
- Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 62 (16): e147-239.
- Pfeffer MA, McMurray JJV, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003; 349 (20): 1893-1906.
- Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358 (15): 1547-1559.
- Flather MD, Yusuf S, Kober L, et al. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet 2000; 355 (9215): 1575-1581.
- Kober L, Torp-Pedersen C, Carlsen JE, et al. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group. N Engl J Med 1995; 333 (25): 1670-1676.
- Yusuf S, Pitt B, Davis CE, Hood WB, Jr., Cohn JN. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 1992; 327 (10): 685-691.
- GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell'infarto Miocardico. Lancet 1994; 343 (8906): 1115-1122.
- Konstam MA, Kronenberg MW, Rousseau MF, et al. Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dilatation in patients with asymptomatic systolic dysfunction. SOLVD (Studies of Left Ventricular Dysfunction) Investigators. Circulation 1993; 88 (5 Pt 1): 2277-2283.
- Palmer SC, Mavridis D, Navarese E, et al. Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis. Lancet 2015; 385 (9982): 2047-2056.
- KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl (2011) 2013; 3 (1): i-150.
- Laffel LM, McGill JB, Gans DJ. The beneficial effect of angiotensin-converting enzyme inhibition with captopril on diabetic nephropathy in normotensive IDDM patients with microalbuminuria. North American Microalbuminuria Study Group. Am J Med 1995; 99 (5): 497-504.
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