Effects of ACE inhibitors in congestive heart failure - adapted from the Journal of the American Med

Date: Oct, 1995

Previous studies have shown that enalapril decreases mortality in patients with congestive heart failure (CHF), but further analysis is needed to determine whether other angiotensin-converting enzyme (ACE) inhibitors could also reduce mortality, and whether specific causes of death could be reduced. Garg and colleagues reviewed a variety of studies that examined the effect of ACE inhibitors on morbidity and mortality.

Randomized, placebo-controlled trials were analyzed if they were at least eight weeks long and determined total mortality by intention to treat. Sample size was not a criterion for exclusion. After excluding some trials in which data were not available in English, or trials in which data were not available on each patient, this analysis used information from 7,105 patients in 32 separate studies. The outcome of interest was most often mortality, but the trials also looked at the effect of the study drugs on exercise capacity and morbidity. Most patients in each trial had advanced CHF (e.g., ejection fraction less than 35 or 40 percent).

A total of 3,870 patients were included in the ACE inhibitor groups and 3,235 patients were included in the various control groups. Of the patients in the control groups, 709 (21.9 percent) died, compared with 611 (15.8 percent) of the patients receiving treatment with an ACE inhibitor. This shows a statistically significant reduction in mortality with treatment (odds ratio: 0.77). No appreciable difference in reduction in mortality was found among the different study drugs (although little data were available for benazepril, cilazapril and perinodopril).

The authors also examined the longer term effect of treatment with the ACE inhibitors. Most of the reduction in mortality occurred in the first three months of the study, and this reduction was significant. Beyond the first 90 days, additional benefit seemed to occur, although the reduction in mortality was not significant. The odds of hospitalization or death due to CHF was 0.65 for patients who received study drugs compared with patients in the control groups (22.4 percent versus 32.6 percent). The most common cause of death was progressive CHF, with subsequent arrhythmia, infarction, cerebrovascular accident or pulmonary emboli. Most of the reduction in mortality was related to a decrease in the number of deaths due to progressive CHF. When different subgroups were analyzed with respect to age, functional ability, sex and cause of CHF, patients who seemed to benefit the most were those with very low ejection fractions (less than 0.25).

These data concur with the results of previous trials, in that the chance of death or hospitalization due to CHF is reduced by treatment with ACE inhibitors. The only statistically significant reduction was seen with enalapril, but similar trends were observed in patients receiving other agents. Whether these benefits will be seen in patients with less compromised left ventricular function remains uncertain. The specific recommendation is that patients with CHF (especially those with low ejection fractions) should, barring contraindications, be started on ACE inhibitors early in the course of their disease. (JAMA, May 10, 1995, vol. 273, p. 1450.)

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