Review: Survival benefit for early ACE inhibitor therapy is greater in some subgroups of patients with acute MI
ACP J Club. 1998 Nov-Dec; 129:57. doi:10.7326/ACPJC-1998-129-3-057
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ACE Inhibitor Myocardial Infarction Collaborative Group. Indications for ACE inhibitors in the early treatment of acute myocardial infarction: systematic overview of individual data from 100 000 patients in randomized trials. Circulation. 1998Jun 9;97:2202-12.
In patients with acute myocardial infarction (MI), are there subgroups of patients for whom the benefits of early angiotensin-converting enzyme (ACE) inhibitors are greater?
Studies were included if they were randomized controlled trials that compared ACE inhibitor therapy started in the acute phase (0 to 36 h) of MI with no routine ACE inhibitor therapy and if they included > 1000 patients (98% of all randomized patients were included in these trials).
Principal investigators of all of the trials formed a collaborative group to collate individual patient data for end points, which included death, nonfatal heart failure, and ventricular fibrillation. Data were checked for completeness and for consistency with the published results.
4 trials with individual patient data for 98 496 patients (mean age 63 y, 75% men) met the inclusion criteria. 2 trials used captopril, 1 used enalapril, and 1 used lisinopril. 3 trials were placebo-controlled, and 1 used an open control. Treatment duration was 28 days in 2 trials, 42 days in 1 trial, and 6 months in 1 trial. By 30 days, fewer deaths had occurred in patients receiving ACE inhibitors than in controls (P < 0.004) (Table); most of the benefit occurred in the first few days. Subgroup analysis showed a greater proportional survival benefit amongpatients 55 to 74 years of age (P ≥ 100 beats/min, and patients with evidence of anterior MI. Absolute survival benefit was higher among patients at high risk for events (Killip class 2 and 3, heart rate > 100 beats/min, and anterior MI). No benefit was detected among persons ≥ 75 years of age. Fewer episodes of heart failure occurred in the ACE inhibitor group than in the control group (P = 0.01) (Table). No difference existed for ventricular fibrillation. Patients who received ACE inhibitors had higher rates of adverse events, including persistent hypotension (17.6% vs 9.3%, P < 0.05), renal dysfunction (1.3% vs 0.6%, P < 0.05), cardiogenic shock (3.9% vs 3.5%, P < 0.05), and second- and third-degree heart block (4.2% vs 3.7%, P < 0.05).
Early angiotensin-converting enzyme inhibitor therapy reduces 30-day mortality and heart failure in patients with acute myocardial infarction. The absolute survival benefit is greatest among high-risk patients.
Sources of funding: Canadian Medical Research Council; Astra; Bristol-Myers Squibb; Hoechst Marion Roussel; Merck; Zeneca.
For correspondence: Dr. M.G. Franzosi, ACE Inhibitor Collaborative Group, GISSI Coordinating Centre, Istituto di Ricerche Farmacologiche “Mario Negri,” Via Eritrea 62, 20157 Milano, Italy. FAX 39-2-332-00049.
Table. Angiotensin-converting enzyme (ACE) inhibitors vs control at 30 days in patients with acute myocardial infarction*
|Outcomes||ACE inhibitors||Control||RRR (95% CI)||NNT (CI)|
|Death||7.1%||7.6%||6% (2 to 10)||210 (125 to 662)|
|Nonfatal heart failure||14.6%||15.2%||4% (1 to 7)||165 (111 to 488)|
*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.
Therapy with ACE inhibitors has been shown to improve survival in patients with asymptomatic left ventricular dysfunction and symptomatic heart failure, with benefit roughly proportional to the degree of risk in the population studied. The series of megatrials included in this meta-analysis sought to test the benefit of ACE inhibitors in a general population after MI rather than in patients with heart failure, in the coronary care setting rather than later after MI, and with treatment for the first few weeks after MI rather than for months or years.
As expected, the trials showed a much more modest overall benefit than did previous trials involving sicker patients. Patients should be considered for early ACE inhibitor therapy after MI if the location of the MI is anterior or if any signs of left ventricular dysfunction (such as clinically defined heart failure manifested by lung rales or, in some cases, tachycardia) are present. Elderly patients should not be excluded.
This study also addresses the timing ofinitiation of ACE inhibitor therapy. Because 40% of the benefit in 30-day mortality occurred in the first day, the therapy should be considered during the early hours after presentation. However, if borderline hypotension dictates delay of ACE inhibitor therapy, this therapy should be reconsidered when blood pressure improves. The benefit of ACE inhibitors seems to be a class effect; no advantage for any specific agent has been shown.
An important question that was not addressed by the analysis is the interaction of ACE inhibitors with β-blockers, which have also been shown to preferentially benefit high-risk patients and are complementary to ACE inhibitors (1, 2). It is probably worthwhile to initiate both agents early in low doses with up-titration as tolerated.
Steven Borzak, MD
Henry Ford Hospital and Medical CenterDetroit, Michigan, USA
Steven Borzak, MD
Henry Ford Hospital and Medical Center
Detroit, Michigan, USA
2. Pfeffer MA, Braunwald E, Moye 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;327:669-77.