Predictors of decreased renal function in patients with hear, failure during angiotensin-converting enzyme inhibitor therapy: Results from the Studies of Left Ventricular Dysfunction (SOLVD)

Background Although angiotensin-converting enzyme inhibitor therapy reduces mortality rates in patients with congestive heart failure (CHF), it may al so cause decreased renal function. Little information is available to predi ct which patients are at highest risk for this complication. Objective To quantify specific clinical predictors of reduction in renal fu nction in patients with CHF who are prescribed angiotensin-converting enzym e inhibitor therapy. Method We analyzed data from the Studies of Left Ventricular Dysfunction (S OLVD), a randomized, double-blind, placebo-controlled trial of enalapril fo r the treatment of CHF. There were 3379 patients randomly assigned to enala pril with a median follow-up of 974 days and 3379 patients randomly assigne d to placebo with a mean follow-up of 967 clays. Decreased renal function w as defined as a rise in serum creatinine greater than or equal to 0.5 mg/dL (44 mu mol/L) From baseline. We used time-to-event analysis to identify po tential predictors of decrease in renal function including age, baseline el ection fraction, baseline creatinine, low systolic blood pressure (<100 mm Hg), history of hypertension, diabetes, and use of antiplatelet, diuretic, and beta-blocker therapy. Results Patients randomly assigned to enalapril had a 33% greater likelihoo d of decreased renal function than controls (P = .003). By multivariate ana lysis, in both the placebo and enalapril groups older age, diuretic therapy , and diabetes were associated with decreased renal function, whereas beta- blocker therapy and higher ejection fraction were renoprotective. Older age was associated with a greater risk of developing decreased renal function in both groups, but significantly more so in the enalapril group (enalapril : risk ratio [RR] 1.42 per 10 years, 95% confidence interval [CI] 1.32-1.52 with enalapril; placebo: RR 1.18, 95% CI 1.12-1.25). Diuretic therapy was likewise associated with a greater risk of decreased renal function in the enalapril group (RR 1.89, 95% CI 1.70-2.08) than in the placebo group (RR 1 .35, 95% CI 1.09-1.66). Conversely, enalapril had a relative renoprotective effect (RR 1.33, 95% CI 1.13-1.53) compared with placebo (RR 1.96, 95% CI 1.57-2.44) in patients with diabetes. A lower risk of renal impairment was seen in both groups with beta-blocker therapy (RR 0.70, 95% CI 0.57-0.85) a nd higher baseline ejection fraction (RR 0.93 per 5% increment, 95% CI 0.91 -0.96). Conclusions Enalapril use caused a 33% increase in the risk of decreased re nal function in patients with CHF. Diuretic use and advanced age increased this risk. Diabetes was associated with an increased risk of renal impairme nt in all patients with CHF, but this risk was reduced in the enalapril gro up compared with the placebo group. beta-Blocker therapy and higher ejectio n fraction were renoprotective in all patients regardless of therapy.