A RANDOMIZED PLACEBO-CONTROLLED TRIAL OF COMBINED EARLY INTRAVENOUS CAPTOPRIL AND RECOMBINANT TISSUE-TYPE PLASMINOGEN-ACTIVATOR THERAPY IN ACUTE MYOCARDIAL-INFARCTION

The adjunctive use of intravenous captopril with tissue plasminogen activator early during acute myocardial infarction offers theoretic advantages of diminishing left ventricular volume, preventing ventricular dilation and improving patient survival. To test the safety and efficacy of combined early administration of intravenous captopril and recombinant tissue-type plasminogen activator (rt-PA), 38 patients treated with rt-PA 3 +/- 0.3 h (mean +/- SE) after the onset of myocardial infarction were randomized to intravenous followed by oral captopril or placebo therapy. They underwent cardiac catheterization with measurement of hemodynamic variables and left ventricular function and determination of serum renin, angiotensin and aldosterone levels on days 1 and 7. Oral administration of the selected agent was continued for 3 months along with other antianginal medications, including nonangiotensin-converting enzyme inhibitor vasodilators. Repeat measurements of left ventricular function were obtained before hospital discharge and at 3 months. There were no significant differences in baseline clinical characteristics between groups. One patient in the captopril-treated group became hypotensive during intravenous therapy, requiring discontinuation of treatment. Compared with the placebo-treated group, the captopril-treated group had significant reductions at day 7 in left ventricular end-diastolic pressure (22.5 +/- 1.5 versus 16.3 +/- 1.6 mm Hg, p < 0.01) and mean systemic arterial pressure (93.6 +/- 3.3 versus 86.2 +/- 2.7 mm Hg, p < 0.05). Although left ventricular ejection fraction did not differ between groups at day 7, left ventricular end-diastolic volume increased significantly in placebo-treated patients (134.8 +/- 9.7 versus 155.9 +/- 9.4 ml, p = 0.02) but decreased slightly in the captopril-treated group (144.6 +/- 13.6 versus 136.5 +/- 10.4 ml, p = NS). End-systolic volume increased over the first week in the placebo-treated group (70.4 +/- 6.6 versus 74.3 +/- 7.2 ml) and decreased in the captopril-treated patients (74.9 +/- 10.3 versus 67.4 +/- 7.3 ml), although these trends were not significant. In conclusion, the early combined use of intravenous captopril and rt-PA after acute myocardial infarction appears safe and may prevent ventricular enlargement.