Predictors of decreased renal function in patients with heart 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 also cause decreased renal function. Little information is available to predict which patients are at highest risk for this complication.


OBJECTIVE
To quantify specific clinical predictors of reduction in renal function in patients with CHF who are prescribed angiotensin-converting enzyme inhibitor therapy.


METHODS
We analyzed data from the Studies of Left Ventricular Dysfunction (SOLVD), a randomized, double-blind, placebo-controlled trial of enalapril for the treatment of CHF. There were 3379 patients randomly assigned to enalapril with a median follow-up of 974 days and 3379 patients randomly assigned to placebo with a mean follow-up of 967 days. Decreased renal function was defined as a rise in serum creatinine >/=0.5 mg/dL (44 micromol/L) from baseline. We used time-to-event analysis to identify potential predictors of decrease in renal function including age, baseline ejection 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 likelihood of decreased renal function than controls (P =.003). By multivariate analysis, 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) and 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 renal function in patients with CHF. Diuretic use and advanced age increased this risk. Diabetes was associated with an increased risk of renal impairment in all patients with CHF, but this risk was reduced in the enalapril group compared with the placebo group. beta-Blocker therapy and higher ejection fraction were renoprotective in all patients regardless of therapy.
Knight
E L
EL
Division of Pharmacoepidemiology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Glynn
R J
RJ
McIntyre
K M
KM
Mogun
H
H
Avorn
J
J
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D004232:Diuretics / Q000627:therapeutic use; D004656:Enalapril / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D013318:Stroke Volume / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D004656:Enalapril; D003404:Creatinine