Key result
Long-term captopril improves 1-year survival by ~27% absolute vs placebo in rats with experimental MI.
Why the study?
There was no evidence that vasodilator therapy could prolong survival after myocardial infarction despite improving functional capacity in congestive heart failure.
Does long-term therapy with captopril improve survival in rats after experimental myocardial infarction?
RCT (n=302)
randomly assigned
Does long-term therapy with captopril improve survival in rats after experimental myocardial infarction?
Absolute Event Rate: 48% vs 21%
p-value: p=<0.02
In a rat model of myocardial infarction, long-term captopril therapy significantly prolonged survival, providing early experimental evidence for ACE inhibitor use post-MI.
Supports ACEI investigation in experimental MI models; leaves open human translation pending clinical trials.
Although vasodilator therapy has been shown to improve functional capacity in patients with congestive heart failure, there is no evidence that such therapy can prolong survival. Coronary artery ligation in the rat was used to produce a wide range of myocardial infarct sizes and a resultant spectrum of left ventricular dysfunction. To determine the relationship between size of myocardial infarction and long-term survival and to test the hypothesis that long-term therapy with captopril could improve survival after myocardial infarction, 302 rats were randomly assigned to either placebo or captopril therapy 14 days after coronary artery ligation. The animals were kept in a laminar flow unit and followed daily for a 1 year period or until spontaneous death. Size of myocardial infarction was determined by planimetry of serial histologic sections of the left ventricle. One year survival in placebo-treated rats decreased markedly in direct relation to increasing size of infarction (from 71% in noninfarcted rats to only 8% in rats with large infarcts). Long-term captopril therapy prolonged the survival of rats with infarcts (p less than .02). The most marked improvement in survival was noted in the animals with infarcts of moderate size, in which 1 year survival was 21% in the placebo-treated rats and 48% in the captopril-treated rats. Thus, in this experimental preparation of myocardial infarction and left ventricular dysfunction, survival was inversely related to size of infarction. Long-term therapy with captopril, which we had previously shown to improve left ventricular function and lessen dilatation in the chronic phase of infarction, also had a pronounced effect on prolonging survival in this preparation of chronic infarction.
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Pfeffer et al. (1985) conducted an RCT in experimental myocardial infarction (n=302). captopril vs. placebo was evaluated on 1 year survival (p=<0.02). Long-term captopril therapy prolonged 1-year survival in rats with experimental myocardial infarction compared to placebo (P<0.02), improving survival from 21% to 48% in moderate-sized infarcts.