Effects of early treatment with captopril and metoprolol singly or together on six-month mortality and morbidity after acute myocardial infarction. Results of the RIMA (Rimodellamento Infarto Miocardico Acuto) study. The RIMA researchers.

Unlabelled: The RIMA (Rimodellamento Infarto Miocardico Acuto) study was designed to assess the relative effects of angiotensin-converting enzyme (ACE) inhibition by captopril, beta-blocker therapy by metoprolol, and their combination in patients with a first acute myocardial infarction on: 1. echocardiographically detected left ventricular remodeling; 2. prognosis. The second goal will be the argument of the present paper. Two-hundred fifty < or = 75 years consecutive patients (mean age: 58 yrs, males = 203) with acute myocardial infarction were randomly allocated to receive for > or = 3 months captopril (up to 75 mg/day, Group 1), metoprolol (up to 200 mg/day, Group 2) or captopril + metoprolol (Group 3) starting in the first 24 hours after the onset of symptoms. Intravenous beta-blockers in the acute phase of myocardial infarction and all other cardioactive drugs were allowed. The effect of the randomized therapy at six months from admission to the coronary care unit was considered in relation to: 1. recurrence of spontaneous cardiac events and of elective revascularization procedures; 2. adverse reactions (hypotension, atrioventricular block, cough, allergy, need of beta-blockers in Group 1, need for ACE inhibition in Group 2) requiring treatment modification based on physician's decision.
Results: Definite follow-up data were available in 226 patients and 195/226 patients (86%) had a complete treatment period. In these patients (per protocol analysis), 37 spontaneous cardiac events occurred: cardiac death = 6, non-fatal reinfarction = 9, unstable angina requiring hospitalization = 16, congestive heart failure = 6. Moreover, seven patients received a coronary revascularization procedure. Events occurred in 11/67 patients from Group 1, 16/63 patients from Group 2, 10/65 patients from Group 3 (16% vs 25% vs 15%, p = 0.28). The multiple logistic regression analysis demonstrated an increased odds ratio (OR) for spontaneous cardiac events in patients from Group 2 (OR = 2.82, 95% Cl: 1.16-6.87: p < 0.05). Elective revascularization procedures were statistically less frequent in patients treated with metoprolol (Group 1 = 9%, Group 2 = 1.6%, Group 3 = 0%; Group 1 vs Groups 2 and 3; p = 0.03). The intention-to-treat analysis on the overall population (226 patients) confirmed the presence of a trend towards a higher risk in patients from Group 2 (OR = 2.1, 95% Cl: 0.96-4.59; p = 0.06). Adverse reactions were observed in 16 patients from Group 1, 6 patients from Group 2 and 15 patients from Group 3 (22% vs 10% vs 23%; Group 2 vs Groups 1 and 3; p = 0.08). At the multivariate regression analysis, a trend towards less adverse reactions in patients assigned to the beta-blocker therapy alone was confirmed (OR = 0.41, 95% Cl: 0.15-1.13; p = 0.07).
Conclusions: In a randomized early post-infarction treatment strategy, ACE inhibition with captopril alone or in combination with metoprolol demonstrated an increased protection against spontaneous cardiac events at six months in comparison with metoprolol alone. On the other hand, the beta-blocker treatment was associated with a lower number of elective revascularization procedures and appeared better tolerated than ACE inhibition.