Can people with heart disease take an angiotensin-converting enzyme (ACE) inhibitor?

The renin-angiotensin-aldosterone system is a key component in the development of cardiovascular disease and high blood pressure.^1-3 Heart failure (HF) management guidelines recommend the inhibition of angiotensin by an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) is a key component of the treatment plan for people with hypertension and heart failure with reduced ejection fraction (HFrEF).^2-4 Studies have shown ACE inhibitors may reduce HF hospitalizations and death in people with HFrEF.^5-9

The 2017 American College of Cardiology (ACC) and American Heart Association (AHA) hypertension guidelines recommends:¹⁰

• 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)].¹⁰
• 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)].¹⁰
• 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)].¹⁰

The 2016 American College of Cardiology Foundation (ACCF) and AHA update to the 2013 guidelines recommend ACE inhibitors as a primary choice for renin-angiotensin system inhibition for patients with current or prior symptoms of HFrEF to reduce morbidity and mortality.³ The 2013 ACCF/AHA guidelines recommend ACE inhibitors to prevent HF in patients all patients with reduced ejection fraction, regardless of whether they have a history of myocardial infarction (MI) or not.⁴

The 2010 Heart Failure Society of America HF practice guideline recommends ACE inhibitors for all people with asymptomatic reduced left ventricular ejection fraction (<40%).¹¹

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 six weeks following an acute MI.¹² 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 1987 double-blind randomized controlled trial of enalapril with 253 patients with severe HF, found a 27% (p=0.003) reduction in total mortality in the treated group versus the placebo group.¹³ A significant improvement with reduction of heart size and reduced need for other HF medication was seen in the enalapril group.

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.¹⁴ Radionuclide end-diastolic volume decreased in enalapril patients (120 ± 25 to 113 ± 25 mL/m^2, mean ± SD) increased in placebo patients (119 ± 28 to 124 ± 33 mL/m²).

Captopril, enalapril, fosinopril, lisinopril, and quinapril are approved to treat HF.^15-19 Ramipril and trandolapril are approved to treat symptomatic HF in stable patients within the first few days following MI.^19-21 Captopril and trandolapril are approved to treat left ventricular dysfunction following MI and enalapril is approved for asymptomatic left ventricular dysfunction.^16,17,20 Lisinopril is approved to reduce the signs and symptoms of HF in people who are not responding adequately to diuretics and digitalis.²² Lisinopril is indicated to reduce mortality in treatment of stable patients within 24 hours of acute MI.²²

Manufacturers recommend monitoring renal function and potassium levels in people with HF taking ACE inhibitors.^15-25

^References

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. Lindenfeld J, Albert NM, Boehmer JP, et al. HFSA 2010 comprehensive heart failure practice guideline. J Card Fail 2010; 16 (6): e1-194.
12. 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.
13. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987; 316 (23): 1429-1435.
14. 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.
15. Fosinopril sodium [package insert]. Miami, FL: Ciplo USA Inc; 2015.
16. Vasotec [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; 2015.
17. Capoten [package insert]. Spring Valley, NY: Par Pharmaceutical Companies, Inc.; 2012.
18. Accupril [package insert]. New York, NY: Parke Davis, Pfizer; 2017.
19. Angiotensin-converting enzyme inhibitors. Drug Facts and Comparisons [online database]. Wolters Kluwer Health, Inc; 2017. Accessed Oct 8, 2017.
20. Trandolapril [package insert]. Laurelton, NY: Epic Pharma, LLC; 2017.
21. Altace [package insert]. New York, NY: Pfizer Laboratories; 2017.
22. Prinivil [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2016.
23. Lotensin [package insert]. Parsippany, NJ: Validus Pharmaceuticals LLC; 2014.
24. Aceon [package insert]. North Chicago, IL: Abbot Laboratories; 2011.
25. Moexipril hydrochloride [package insert]. Teva Pharmaceuticals USA Inc; 2016.