Effects of enalapril in systolic heart failure patients with and without chronic kidney disease: Insights from the SOLVD Treatment trial

BackgroundAngiotensin-converting enzyme inhibitors improve outcomes in systolic heart failure (SHF). However, doubts linger about their effect in SHF patients with chronic kidney disease (CKD).MethodsIn the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial, 2569 ambulatory chronic HF patients with left ventricular ejection fraction ≤ 35% and serum creatinine level ≤ 2.5 mg/dl were randomized to receive either placebo (n = 1284) or enalapril (n = 1285). Of the 2502 patients with baseline serum creatinine data, 1036 had CKD (estimated glomerular filtration rate < 60 ml/min/1.73 m2).ResultsOverall, during 35 months of median follow-up, all-cause mortality occurred in 40% (502/1252) and 35% (440/1250) of placebo and enalapril patients, respectively (hazard ratio {HR}, 0.84; 95% confidence interval {CI}, 0.74-0.95; p = 0.007). All-cause mortality occurred in 45% and 42% of patients with CKD (HR, 0.88; 95% CI, 0.73-1.06; p = 0.164), and 36% and 31% of non-CKD patients (HR, 0.82; 95% CI, 0.69-0.98; p = 0.028) in the placebo and enalapril groups, respectively (p for interaction = 0.615). Enalapril reduced cardiovascular hospitalization in those with CKD (HR, 0.77; 95% CI, 0.66-0.90; p < 0.001) and without CKD (HR, 0.80; 95% CI, 0.70-0.91; p < 0.001). Among patients in the enalapril group, serum creatinine elevation was significantly higher in those without CKD (0.09 versus 0.04 mg/dl in CKD; p = 0.003) during first year of follow-up, but there was no differences in changes in systolic blood pressure (mean drop, 7 mm Hg, both) and serum potassium (mean increase, 0.2 mEq/L, both).ConclusionsEnalapril reduces mortality and hospitalization in SHF patients without significant heterogeneity between those with and without CKD.