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

Angiotensin-converting enzyme (ACE) inhibitors are approved for use in the US by the FDA for the treatments outlined in the table below.^1-14 Ramipril is also approved to reduce the risk of myocardial infarction (MI), stroke, or death from cardiovascular causes.¹³

Table 1: FDA approved ACE inhibitor use

*Brand names with asterisks beside them have been discontinued in the US. The generic versions of these drugs continue to be FDA approved and are available in the US.

**Ramipril and trandolapril are approved to treat heart failure following myocardial infarction.

The renin-angiotensin-aldosterone system is a key component in both the development of cardiovascular disease and high blood pressure. Angiotensin-converting enzyme (ACE) inhibitors are effective in reducing initial ischemic heart disease (IHD) events, recommended for consideration in all patients after myocardial infarction (MI), and proven to prevent and improve heart failure (HF). HF management guidelines recommend the inhibition of angiotensin by an ACE inhibitor or angiotensin II receptor blocker (ARB) as a key component of the treatment plan for people with hypertension and reduced ejection fraction (HFrEF).^15-17 Studies have shown ACE inhibitors may reduce HF hospitalizations and death in people with HFrEF.^18-22

The 2017 ACC/AHA hypertension guidelines recommend:

• Adults with stable IHD and hypertension (blood pressure [BP] ≥ 130/80 mm Hg) should be treated with ACE inhibitors, ARBs, or beta blockers as first-line therapy (Class of Recommendation [COR] I, Level of Evidence [LOE] B-Randomized [R]).*
• Adults with heart failure with preserved ejection fraction (HFpEF) and persistent hypertension after management of volume overload should be prescribed ACE inhibitors or ARBs and beta blockers titrated to attain a systolic BP of less than 130 mm Hg (COR I, LOE C- Expert Opinion [EO]).
• For adults who experience a stroke or transient ischemic attack, treatment with an ACE inhibitor, ARB, or thiazide diuretic is useful (COR I, LOE A).
• In adults with diabetes mellitus and hypertension, all first-line classes of antihypertensive agents including ACE inhibitors, ARBS, calcium channel blockers (CCBs), and diuretics are useful and effective (COR I, LOE A). ²³

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. 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]).²⁴

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.²⁵

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

Manufacturers warn that patients whose renal function may depend on the activity of the renin-angiotensin system such as those severe congestive heart failure, post-myocardial infarction, or volume depletion may be at particular risk of developing acute renal failure on an ACE inhibitor. Patients at increased risk of excessive hypotension while taking an ACE inhibitor include those with heart failure with systolic blood pressure below 100 mm Hg, ischemic heart disease, or cerebrovascular disease. ^1-14

*See ACC/AHA Class of Recommendation and Level of Evidence definitions below:

References

1. Lotensin [package insert]. Parsippany, NJ: Validus Pharmaceuticals LLC; 2019.
2. Capoten [package insert]. Chestnut Ridge, NY: Par Pharmaceutical; 2017.
3. Epaned [package insert]. Wilmington, MA: Azurity Pharmaceuticals, Inc.; 2020.
4. Vasotec [package insert]. Bridgewater, NJ: Bausch Health US LLC; 2018.
5. Enalaprilat [package insert]. Lake Forest, IL: Hospira, Inc.; 2021.
6. Monopril [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2003.
7. Qbrelis [package insert]. Wilmington, MA: Azurity Pharmaceuticals, Inc.; 2020.
8. Prinivil [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2021.
9. Zestril [package insert]. Morristown, NJ: Almatica Pharma LLC; 2020.
10. Univasc [package insert]. Smyrna, GA: USB, Inc; 2012.
11. Aceon [package insert]. Cincinnati, OH: Patheon Pharmaceuticals, Inc.; 2017.
12. Accupril [package insert]. New York, NY: Parke Davis, Pfizer; 2021.
13. Altace [package insert]. New York, NY: Pfizer Laboratories; 2022.
14. Mavik [package insert]. Whippany, NJ: Halo Pharmaceutical Inc.; 2017.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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. Hypertension 2017.
24. 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.
25. 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.
26. 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.