Angiotensin converting enzyme inhibitors and receptor blockers in acute myocardial infarction: Clinical trials
- Guy S Reeder, MD
Guy S Reeder, MD
- Section Editor — Coronary Disease
- Professor of Medicine
- Mayo Medical School
A number of therapies are beneficial in the management of patients with acute myocardial infarction (MI), including revascularization with either percutaneous coronary intervention or fibrinolysis, aspirin, beta blockers, statins, and either angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). (See "Overview of the acute management of ST elevation myocardial infarction" and "Overview of the acute management of unstable angina and non-ST elevation myocardial infarction".)
The evidence supporting the efficacy of ACE inhibitors and ARBs in this setting will be reviewed here. Recommendations for the use of ACE inhibitors and ARBs after MI, the use of ACE inhibitors in patients with heart failure due to systolic dysfunction, and the mechanisms by which ACE inhibitors might act are discussed separately. (See "Angiotensin converting enzyme inhibitors and receptor blockers in acute myocardial infarction: Recommendations for use" and "Angiotensin converting enzyme inhibitors in acute myocardial infarction: Mechanisms of action" and "ACE inhibitors in heart failure with reduced ejection fraction: Therapeutic use".)
ACE INHIBITOR EFFECTS ON CARDIAC FUNCTION AND MORTALITY
Most randomized trials have demonstrated that angiotensin converting enzyme (ACE) inhibitor therapy with captopril, enalapril, ramipril, trandolapril, or zofenopril started within 24 hours to 16 days following an acute myocardial infarction (MI) improves the left ventricular ejection fraction (LVEF) at one month to one year [1-14]. In these studies, the great majority of patients had an ST elevation MI (STEMI); data are limited in patients with a non-ST elevation MI (NSTEMI) . In addition, most patients were treated with either fibrinolytic therapy or no reperfusion; data in patients who underwent percutaneous coronary intervention (PCI) for MI are limited.
The administration of an ACE inhibitor is also associated with an important improvement in patient survival. Large (50 lives saved per 1000 patients treated) mortality benefits post-MI have been demonstrated in patients with low LVEF, heart failure (HF), or anterior MIs. Smaller benefits (five lives saved per 1000 treated) have been found in low-risk patients.
The benefits derived from ACE inhibition in high-risk patients are generally greater than those achieved by other therapeutic interventions. As an example, a meta-analysis of the nine largest randomized prospective trials comparing intravenous fibrinolysis versus placebo demonstrated approximately 30 lives were saved per 1000 patients treated who presented within six hours of symptom onset. However, the effect of these other interventions are additive to those associated with ACE inhibition.
- Pfeffer MA, Lamas GA, Vaughan DE, et al. Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med 1988; 319:80.
- Sharpe N, Smith H, Murphy J, et al. Early prevention of left ventricular dysfunction after myocardial infarction with angiotensin-converting-enzyme inhibition. Lancet 1991; 337:872.
- St John Sutton M, Pfeffer MA, Plappert T, et al. Quantitative two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction. The protective effects of captopril. Circulation 1994; 89:68.
- Schulman SP, Weiss JL, Becker LC, et al. Effect of early enalapril therapy on left ventricular function and structure in acute myocardial infarction. Am J Cardiol 1995; 76:764.
- Pfeffer MA, Braunwald E, Moyé LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 1992; 327:669.
- Wright RA, Flapan AD, Alberti KG, et al. Effects of captopril therapy on endogenous fibrinolysis in men with recent, uncomplicated myocardial infarction. J Am Coll Cardiol 1994; 24:67.
- Køber 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; 333:1670.
- Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Lancet 1993; 342:821.
- Hall AS, Murray GD, Ball SG. Follow-up study of patients randomly allocated ramipril or placebo for heart failure after acute myocardial infarction: AIRE Extension (AIREX) Study. Acute Infarction Ramipril Efficacy. Lancet 1997; 349:1493.
- Ambrosioni E, Borghi C, Magnani B. The effect of the angiotensin-converting-enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. The Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study Investigators. N Engl J Med 1995; 332:80.
- van Gilst WH, Kingma JH, Peels KH, et al. Which patient benefits from early angiotensin-converting enzyme inhibition after myocardial infarction? Results of one-year serial echocardiographic follow-up from the Captopril and Thrombolysis Study (CATS). J Am Coll Cardiol 1996; 28:114.
- Swedberg K, Held P, Kjekshus J, et al. Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction. Results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II). N Engl J Med 1992; 327:678.
- Oral captopril versus placebo among 13,634 patients with suspected acute myocardial infarction: interim report from the Chinese Cardiac Study (CCS-1). Lancet 1995; 345:686.
- ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. Lancet 1995; 345:669.
- 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; 343:1115.
- Six-month effects of early treatment with lisinopril and transdermal glyceryl trinitrate singly and together withdrawn six weeks after acute myocardial infarction: the GISSI-3 trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico. J Am Coll Cardiol 1996; 27:337.
- Ferguson JJ. Meeting highlights. Highlights of the 20th congress of the European society of cardiology. Circulation 1999; 99:1127.
- Zuanetti G, Latini R, Maggioni AP, et al. Effect of the ACE inhibitor lisinopril on mortality in diabetic patients with acute myocardial infarction: data from the GISSI-3 study. Circulation 1997; 96:4239.
- Rutherford JD, Pfeffer MA, Moyé LA, et al. Effects of captopril on ischemic events after myocardial infarction. Results of the Survival and Ventricular Enlargement trial. SAVE Investigators. Circulation 1994; 90:1731.
- Torp-Pedersen C, Køber L. Effect of ACE inhibitor trandolapril on life expectancy of patients with reduced left-ventricular function after acute myocardial infarction. TRACE Study Group. Trandolapril Cardiac Evaluation. Lancet 1999; 354:9.
- Buch P, Rasmussen S, Abildstrom SZ, et al. The long-term impact of the angiotensin-converting enzyme inhibitor trandolapril on mortality and hospital admissions in patients with left ventricular dysfunction after a myocardial infarction: follow-up to 12 years. Eur Heart J 2005; 26:145.
- Cleland JG, Erhardt L, Murray G, et al. Effect of ramipril on morbidity and mode of death among survivors of acute myocardial infarction with clinical evidence of heart failure. A report from the AIRE Study Investigators. Eur Heart J 1997; 18:41.
- Borghi C, Marino P, Zardini P, et al. Short- and long-term effects of early fosinopril administration in patients with acute anterior myocardial infarction undergoing intravenous thrombolysis: results from the Fosinopril in Acute Myocardial Infarction Study. FAMIS Working Party. Am Heart J 1998; 136:213.
- Baur LH, Schipperheyn JJ, van der Wall EE, et al. Beneficial effect of enalapril on left ventricular remodelling in patients with a severe residual stenosis after acute anterior wall infarction. Eur Heart J 1997; 18:1313.
- de Kam PJ, Voors AA, van den Berg MP, et al. Effect of very early angiotensin-converting enzyme inhibition on left ventricular dilation after myocardial infarction in patients receiving thrombolysis: results of a meta-analysis of 845 patients. FAMIS, CAPTIN and CATS Investigators. J Am Coll Cardiol 2000; 36:2047.
- Rodrigues EJ, Eisenberg MJ, Pilote L. Effects of early and late administration of angiotensin-converting enzyme inhibitors on mortality after myocardial infarction. Am J Med 2003; 115:473.
- Flather MD, Yusuf S, Køber 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; 355:1575.
- Latini R, Tognoni G, Maggioni AP, et al. Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: systematic overview of individual data from 96,712 randomized patients. Angiotensin-converting Enzyme Inhibitor Myocardial Infarction Collaborative Group. J Am Coll Cardiol 2000; 35:1801.
- Indications for ACE inhibitors in the early treatment of acute myocardial infarction: systematic overview of individual data from 100,000 patients in randomized trials. ACE Inhibitor Myocardial Infarction Collaborative Group. Circulation 1998; 97:2202.
- Pilote L, Abrahamowicz M, Rodrigues E, et al. Mortality rates in elderly patients who take different angiotensin-converting enzyme inhibitors after acute myocardial infarction: a class effect? Ann Intern Med 2004; 141:102.
- Hennessy S, Kimmel SE. Is improved survival a class effect of angiotensin-converting enzyme inhibitors? Ann Intern Med 2004; 141:157.
- Budaj A, Cybulski J, Cedro K, et al. Effects of captopril on ventricular arrhythmias in the early and late phase of suspected acute myocardial infarction. Randomized, placebo-controlled substudy of ISIS-4. Eur Heart J 1996; 17:1506.
- Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 1991; 325:303.
- Søgaard P, Gøtzsche CO, Ravkilde J, et al. Ventricular arrhythmias in the acute and chronic phases after acute myocardial infarction. Effect of intervention with captopril. Circulation 1994; 90:101.
- Domanski MJ, Exner DV, Borkowf CB, et al. Effect of angiotensin converting enzyme inhibition on sudden cardiac death in patients following acute myocardial infarction. A meta-analysis of randomized clinical trials. J Am Coll Cardiol 1999; 33:598.
- Dickstein K, Kjekshus J, OPTIMAAL Steering Committee of the OPTIMAAL Study Group. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan. Lancet 2002; 360:752.
- Pfeffer MA, McMurray JJ, 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; 349:1893.
- McMurray J, Solomon S, Pieper K, et al. The effect of valsartan, captopril, or both on atherosclerotic events after acute myocardial infarction: an analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT). J Am Coll Cardiol 2006; 47:726.
- Mann DL, Deswal A. Angiotensin-receptor blockade in acute myocardial infarction--a matter of dose. N Engl J Med 2003; 349:1963.
- ACE INHIBITOR EFFECTS ON CARDIAC FUNCTION AND MORTALITY
- Effects in all patients
- Low ejection fraction
- Heart failure
- Early in anterior wall MI
- - After no reperfusion
- - After fibrinolytic therapy
- Timing of therapy
- Class differences
- Mechanism of action
- ACE INHIBITOR EFFECTS ON ARRHYTHMIA
- Ventricular arrhythmia
- - Effect on sudden death
- Atrial fibrillation
- ANGIOTENSIN II RECEPTOR BLOCKERS
- Comparison to ACE inhibitor
- Combination with ACE inhibitor