Lack of long-term ventricular arrhythmia reduction by enalapril in heart failure

Previous studies have indicated that angiotensin-converting enzyme inhibitors may reduce the frequency of ventricular arrhythmias in patients with heart failure. These reports were mostly small and of short duration. We prospectively studied 734 patients recruited in 11 universities for 1 year who were enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) to determine the long-term effects of enalapril and placebo on the frequency and complexity of ventricular arrhythmias in patients with symptomatic (treatment trial) or asymptomatic (prevention trial) heart failure and depressed left ventricular function (ejection fraction ≤35%). Five hundred fifty-three patients from the prevention trial and 181 from the treatment trial of SOLVD underwent ambulatory electrocardiographic monitoring at baseline, and then at 4 and 12 months of double-blind therapy with either placebo or enalapril (2.5 to 10 mg twice daily). The prospectively defined primary analysis was by intent-to-treat and revealed no significant differences in ventricular premature complexes between the placebo and enalapril groups at baseline (87 ± 13 vs 84 ± 13/hour), 4 months (100 ± 15 vs 85 ± 12/hour), or 12 months (80 ± 12 vs 90 ± 14/hour). Likewise, there was no difference between the placebo and enalapril groups in runs of nonsustained ventricular tachycardia: baseline (8.3 ± 4.1 vs 1.9 ± 0.4 runs/day), 4 months (16 ± 12 vs 7.2 ± 4.1 runs/day), or after 12 months of blinded therapy (11 ± 7.0 vs 6.1 ± 4.4 runs/day). Over the 1 -year trial, an equal number of patients in the placebo and enalapril groups developed new ventricular arrhythmias or had comparable reductions in ventricular arrhythmias which had been present at baseline. Our conclusion is that enalapril has no antiarrhythmic effect in a spectrum of patients with heart failure representing New York Heart Association classes I to III. These observations are consistent with the absence of any observed effect of enalapril on sudden death or hospitalization for arrhythmias in the 6,797 patients enrolled in SOLVD.