Early enalapril therapy in patients with left ventricular systolic dysfunction reduced cardiovascular morbidity and mortality at 15-years in SOLVD

Abstract

Background: In the Studies of Left Ventricular Dysfunction (SOLVD), enalapril therapy in patients with low ejection fractions reduced morbidity and mortality over 3-4 years. We reported here the impact of early in-trial treatment with enalapril on post-trial cardiovascular morbidity and mortality at 15 years in SOLVD. Methods: Among the 558 Belgium patients randomized to enalapril or placebo in SOLVD, data on post-trial deaths and cardiovascular morbid events were collected on all 433 survivors (218 enalapril vs. 215 placebo) at close out. We defined cardiovascular morbid events to include the development of heart failure, myocardial infarction or stroke, or the need for heart transplant, device therapy or revascularization. All patients were placed on enalapril after the trial ended. Results: No patient was lost to follow-up. The median duration of follow-up was 15.5 years from randomization or 12.2 years from close out. Fewer deaths (138 vs. 150 deaths) occurred among patients treated early with enalapril as compared with placebo (63% vs. 70%, Wilcoxon P= 0.01). Deaths or cardiovascular morbid events occurred in 177 (81%) of the enalapril group and 188 (87%) of the placebo group (Wilcoxon P=0.008, Figure). Cox regression modified by the Wei-Lin-Weissfield method to account for repeated events showed that enalapril reduced deaths or development of cardiovascular events by 19% when compared to placebo (HR, 0.81; 95% CI, 0.66 to 0.98; P=0.03). Use of angiotensin-converting enzyme inhibitors post trial was similar between the enalapril and placebo groups (85% vs. 79%, P=0.40). Conclusions: This 15-year follow-up of SOLVD showed that enalapril continued to reduce mortality and serious cardiovascular morbidity in patients with left ventricular systolic dysfunction beyond the original trial period.