Captopril adjuvant therapy to beta-blockers and nitrates improves post-myocardial infarction left ventricular performance.

Abstract

A growing body of data support the beneficial effects of angiotensin-converting enzyme inhibitors in the prevention of cardiac enlargement and improvement of left ventricular function in patients with acute myocardial infarction. However, very little information exists about the direct effect of increased afterload on cardiac performance in these patients and the possible favourable effects of angiotensin-converting enzyme inhibitors as adjunctive treatment to thrombolysis, beta-blockers and nitrates. We have, therefore, studied the effects of captopril as adjuvant therapy to thrombolysis, beta-blockers and nitrates (standard therapy) on left ventricular performance in 77 consecutive patients with uncomplicated Q-wave acute myocardial infarction, by the measurement of the pre-ejection period/left ventricular ejection time ratio before and after (0.25-0.50 mg) phenylephrine administration on the 4th and 30th post-infarction days. Patients were randomized on day 4 either to continue standard therapy alone (group 1, 35 patients) or to receive oral captopril therapy (12.5 mg t.i.d.) in addition to standard therapy (group 2, 42 patients) in a double-blind parallel study. Among the patients of group 1 there was a significant deterioration of left ventricular function after phenylephrine administration. This was shown by an increase of pre-ejection period/left ventricular ejection time ratio only in the subset of patients with ejection fraction < 40%, as measured by contrast ventriculography, on both the 4th and 30th post-infarction days changing from 0.435 +/- 0.070 to 0.528 +/- 0.101, P < 0.01 and from 0.404 +/- 0.098 to 0.515 +/- 0.092, P < 0.02, respectively. In contrast there were no significant changes in patients with ejection fraction > or = 40%. Among patients of group 2, phenylephrine administration induced a significant increase, only on the 4th day, in pre-ejection period/left ventricular ejection time ratio only in the subset of patients with ejection fraction < 40% changing from 0.410 +/- 0.107 to 0.535 +/- 0.102, P < 0.01. In the remaining patients with ejection fraction > or = 40% there were no significant changes on either the 4th or 30th post-infarction days. Furthermore, a significant improvement was observed after phenylephrine administration in the pre-ejection period/left ventricular ejection time ratio between the 4th and 30th post-infarction days, which changed from 0.535 +/- 0.102 on day 4 to 0.368 +/- 0.052 on day 30 (P < 0.004). Also, a four-way ANOVA detected a significant reduction of heart rate in patients with ejection fraction < 40% from day 4 to day 30. The results indicate that: (1) the response of pre-ejection period/left ventricular ejection time ratio after increasing afterload may be a useful non-invasive method for the detection of left ventricular dysfunction in myocardial infarction patients; and (2) captopril adjuvant therapy as compared to thrombolysis, beta-blockers and nitrates alone, after phenylephrine administration, improves the left ventricular performance response in asymptomatic Q-wave post-infarction patients and beneficially affects heart rate. This effect is most pronounced in patients with ejection fraction < 40% whereas those with ejection fraction > or = 40% do not obtain clear benefit.