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Abstract

It is not known whether the treatment of patients with asymptomatic left ventricular dysfunction reduces mortality and morbidity. We studied the effect of an angiotensin-converting--enzyme inhibitor, enalapril, on total mortality and mortality from cardiovascular causes, the development of heart failure, and hospitalization for heart failure among patients with ejection fractions of 0.35 or less who were not receiving drug treatment for heart failure. Patients were randomly assigned to receive either placebo (n = 2117) or enalapril (n = 2111) at doses of 2.5 to 20 mg per day in a double-blind trial. Follow-up averaged 37.4 months. There were 334 deaths in the placebo group, as compared with 313 in the enalapril group (reduction in risk, 8 percent by the log-rank test; 95 percent confidence interval, -8 percent [an increase of 8 percent] to 21 percent; P = 0.30). The reduction in mortality from cardiovascular causes was larger but was not statistically significant (298 deaths in the placebo group vs. 265 in the enalapril group; risk reduction, 12 percent; 95 percent confidence interval, -3 to 26 percent; P = 0.12). When we combined patients in whom heart failure developed and those who died, the total number of deaths and cases of heart failure was lower in the enalapril group than in the placebo group (630 vs. 818; risk reduction, 29 percent; 95 percent confidence interval, 21 to 36 percent; P less than 0.001). In addition, fewer patients given enalapril died or were hospitalized for heart failure (434 in the enalapril group; vs. 518 in the placebo group; risk reduction, 20 percent; 95 percent confidence interval, 9 to 30 percent; P less than 0.001). The angiotensin-converting--enzyme inhibitor enalapril significantly reduced the incidence of heart failure and the rate of related hospitalizations, as compared with the rates in the group given placebo, among patients with asymptomatic left ventricular dysfunction. There was also a trend toward fewer deaths due to cardiovascular causes among the patients who received enalapril.

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Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction.

E Braunwald, F. Parisi, D Vaughan … (1988)

We conducted a double-blind, placebo-controlled trial to determine whether ventricular dilatation continues during the late convalescent phase after myocardial infarction and whether therapy with captopril alters this process. Fifty-nine patients with a first anterior myocardial infarction and a radionuclide ejection fraction of 45 percent or less underwent cardiac catheterization 11 to 31 days after infarction, when they were not in overt congestive heart failure. They were randomly assigned to placebo or captopril and were followed for one year. A repeat catheterization was performed to evaluate interval changes in hemodynamic function and left ventricular volume. Thirty-eight male patients were evaluated with maximal-exercise treadmill tests every three months. No differences were detected at base line in clinical, hemodynamic, or quantitative ventriculographic variables. During one year of follow-up, the end-diastolic volume of the left ventricle increased by a mean [+/- SEM] of 21 +/- 8 ml (P less than 0.02) in the placebo group, but by only 10 +/- 6 ml (P not significant) in the captopril group. The left ventricular filling pressure remained elevated with placebo but decreased (P less than 0.01) with captopril. In a subset of 36 patients who were at high risk for ventricular enlargement because they had persistent occlusion of the left anterior descending coronary artery, captopril prevented further ventricular dilatation (P less than 0.05). Patients given captopril also had increased exercise capacity (P less than 0.05). This preliminary study indicates that after anterior myocardial infarction, ventricular enlargement is progressive and that captopril may attenuate this process, reduce filling pressures, and improve exercise tolerance.

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Treatment of patients with symptomless left ventricular dysfunction after myocardial infarction.

Richard Murphy, Abu S. M. A. Hannan, Lois E. H. Smith … (1988)

In a randomised, double-blind trial 60 patients with left ventricular dysfunction (ejection fraction less than 45%) but without clinical evidence of heart failure 1 week after Q wave myocardial infarction were given captopril 25 mg thrice a day, frusemide 40 mg daily, or placebo. Left ventricular volumes were measured at baseline and at 1, 3, 6, 9, and 12 months with cross-sectional echocardiography and Simpson's rule analysis of standardised apical views. The captopril group showed no significant change in left ventricular end-diastolic volume index but left ventricular end-systolic volume index was significantly reduced and stroke volume index and ejection fraction were significantly increased from 1 month on. In contrast, the frusemide and placebo groups showed significant increases in ventricular volumes, with stroke volume index unchanged and ejection fraction slightly reduced. The changes in the captopril group were significantly different from those in the other groups.