Celecoxib use was associated with a dose-related increase in the composite end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure. In light of recent reports of cardiovascular harm associated with treatment with other agents in this class, these data provide further evidence that the use of COX-2 inhibitors may increase the risk of serious cardiovascular events.
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 < .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. Circulation 72, No. 2, 406-412, 1985. THE DIAGNOSIS of congestive heart failure has a grave prognosis.' 2In the Framingham Study, the 5 year mortality rate was greater than 50% for individuals newly diagnosed as having congestive heart failure.' In more recent studies, the median survival of patients with less clearly defined durations of ventricular dysfunction was often measured in months, not years.3-5 Although congestive heart failure is a syndrome that encompasses multiple etiologies, the severity of the cardiac dysfunction appears to have greater prognostic significance than does the specific cause of disease.4 The use of vasodilators, especially the angiotensin-converting enzyme inhibitors, in the treatment
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