Efficacy of Angiotensin-Converting Enzyme Inhibitors and Angiotensin-Receptor Blockers in Coronary Artery Disease without Heart Failure in the Modern Statin Era: a Meta-Analysis of Randomized-Controlled Trials
- 555 Downloads
Current practice guidelines support the use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARBs) in patients with coronary artery disease (CAD) without heart failure (HF). However, a number of cited trials were performed prior to the era of prevalent statin use. Our objective was to evaluate the effectiveness of ACEi and ARBs in reducing cardiovascular events as well as the impact of statin therapy.
We searched the MEDLINE and EMBASE databases for randomized-controlled trials (1/1/1980 – 8/31/2015) with ACEi or ARBs as the single intervention for patients with CAD without HF. We assessed the outcomes of non-fatal myocardial infarction (MI), stroke, cardiovascular mortality and all-cause mortality. The relationship between these outcomes and the percentages of patients on statin therapy was evaluated using meta-regression analysis.
A total of ten ACEi trials and five ARB trials were included for analysis, with 78,761 patients followed for a mean of 36 months. Treatment with ACEi was associated with decreased non-fatal MI (RR 0.83; 95 % CI 0.75–0.91), stroke (RR 0.76; 95 % CI 0.68–0.86), cardiovascular mortality (RR 0.83; 95 % CI 0.72–0.95), and all-cause mortality (RR 0.86; 95 % CI 0.80–0.93). Treatment with ARBs was associated only with a decreased incidence of stroke (RR 0.92; 95 % CI 0.87–0.98). When adjusted for statin use, there was a trend towards an attenuated effect of ACEi in reducing cardiovascular mortality with increased use of statins (p-value = 0.063).
In CAD patients without HF, ACEi, but not ARBs decreases the risk of non-fatal MI, cardiovascular mortality and all-cause mortality, while both ACEi and ARBs decrease the risk of stroke.
KeywordsAngiotensin-converting enzyme inhibitors Angiotensin-receptor blockers Statin Coronary artery disease
Compliance with ethical standards
Conflicts of Interest
The authors report no relationships that could be construed as a conflict of interest.
- 3.GISSI-3 Investigators, Gruppo Italiano per lo Studio della Sopravvivenza nell’infarto Miocardico. Effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet. 1994;343:1115.Google Scholar
- 4.The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet. 1993;342:821–8.Google Scholar
- 5.Ambrosioni E, Borghi C, Magnani B, The Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study Investigators. The effect of the angiotensin-converting enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. N Engl J Med. 1995;332:80–5.CrossRefPubMedGoogle Scholar
- 6.Pfeffer MA, Greaves SC, Arnold JM, The Healing and Early Afterload Reducing Therapy (HEART) Trial Investigators, et al. Early versus delayed angiotensin-converting enzyme inhibition therapy in acute myocardial infarction. The Healing and Early Afterload Reducing Therapy Trial. Circulation. 1997;95:2643–51.CrossRefPubMedGoogle Scholar
- 16.European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease Investigators. Efficacy on perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomized, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003;362:782–8.CrossRefGoogle Scholar
- 19.Ferrari R, Perindopril and Remodeling in Elderly with Acute Myocardial Infarction Investigators. Effects of angiotensin-converting enzyme inhibition with perindopril on left ventricular remodeling and clinical outcome: results of the randomized Perindopril and Remodeling in Elderly with Acute Myocardial Infarction (PREAMI) Study. Arch Intern Med. 2006;166:659–66.CrossRefPubMedGoogle Scholar
- 20.Borghi C, Ambrosioni E. On behalf of the Survival of Myocardial Infarction Long-term Evaluation (SMILE) Study Group Effects of zofenopril on myocardial ischemia in post–myocardial infarction patients with preserved left ventricular function: The Survival of Myocardial Infarction Long-term Evaluation (SMILE)–ISCHEMIA study. Am Heart J. 2007;153:445e7–14.CrossRefGoogle Scholar
- 22.The Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (TRANSCEND) Investigators. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomized controlled trial. Lancet. 2008;372:1174–83.CrossRefGoogle Scholar
- 25.Al-Mallah MH, Tleyjeh IM, Abdel-Latif AA, Weaver WD. Angiotensin-converting enzyme inhibitors in coronary artery disease and preserved left ventricular systolic function. A systematic review and meta-analysis of randomized controlled trials. J Am Coll Cardiol. 2006;47:1576–83.CrossRefPubMedGoogle Scholar
- 27.Danchin N, Cucherat M, Thuillez C, Durand E, Kadri Z, Steq PG. Angiotensin-converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction: an overview of long-term randomized controlled trials. Arch Intern Med. 2006;166:787–96.CrossRefPubMedGoogle Scholar
- 28.Van Vark LC, Bertrand M, Akkerhius KM, et al. Angiotensin-converting-enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of rennin-angiotensin-aldosterone system inhibitors involving 158,998 patients. Eur Heart J. 2012;33:2088–97.CrossRefPubMedPubMedCentralGoogle Scholar
- 31.Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/ non-ST-elevation myocardial infarction: a report of the American College of Cardiology/ American Heart Association Task Force on practice guidelines. Circulation. 2007;116:148–304.CrossRefGoogle Scholar
- 34.Hamm CW, Bassand JP, Agewall S, et al. ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2011;32:2999–3054.CrossRefPubMedGoogle Scholar
- 36.Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 6:e1000100.Google Scholar
- 37.Review Manager (RevMan) [Computer program], Version 5.0. Copenhagen: The Nordic Cochrane Centre. The Cochrane Collaboration, 2008.Google Scholar