Elsevier

American Heart Journal

Volume 138, Issue 5, November 1999, Pages 849-855
American Heart Journal

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),☆☆,

https://doi.org/10.1016/S0002-8703(99)70009-8Get rights and content

Abstract

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. Method: 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 μmol/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 β-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 β-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 β-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. β-Blocker therapy and higher ejection fraction were renoprotective in all patients regardless of therapy. (Am Heart J 1999;138:849-55.)

Section snippets

Methods

The Studies of Left Ventricular Dysfunction (SOLVD) database was used to investigate specific clinical characteristics related to the development of decreased renal function in patients treated with enalapril for CHF.27 The SOLVD study was a randomized, double-blind, placebo-controlled trial of enalapril for the treatment of CHF. The combined treatment and prevention trials used in this study included 6797 patients who were initially selected based on hospitalization discharge diagnosis and

Results

During a mean follow-up of 779 days, 515 (16%) of 3246 patients in the enalapril group had decreased renal function develop according to the study definition compared with 385 (12%) of 3269 in the placebo group during a mean follow-up of 751 days. Baseline clinical predictors for both groups are presented in Table I.

. Baseline clinical variables of the study population

VariablePlacebo groupEnalapril groupP value
Baseline creatinine (mg/dL)1.2 ± 0.3*1.2 ± 0.3*.48
Baseline ejection fraction (%)27 ± 6

Discussion

Analysis of data from this large randomized, controlled trial of ACE inhibitor use in CHF reveals important new information about clinical predictors of renal insufficiency in patients with CHF. Although some risk factors for decreased renal function, such as age, were expected, we were able to quantify this risk and demonstrate that the enalapril-induced risk of renal impairment increases with advanced age. We also found that enalapril increased the risk of diuretic-associated renal impairment

References (36)

  • The CONSENSUS trial study group

    Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS)

    N Engl J Med

    (1987)
  • MAB Devoy et al.

    Deterioration in renal function associated with angiotensin converting enzyme inhibitor therapy is not always reversible

    J Int Med

    (1992)
  • C Moyses et al.

    Safety of long-term use of lisinopril for congestive heart failure

    Am J Cardiol

    (1992)
  • The large state peer review organization consortium

    Heart failure treatment with angiotensin-converting enzyme inhibitors in hospitalized patients in 10 large states

    Arch Intern Med

    (1997)
  • RS Stafford et al.

    National patterns of angiotensin-converting enzyme inhibitor use in congestive heart failure

    Arch Intern Med

    (1997)
  • F Bridoux et al.

    Acute renal failure after the use of angiotensin converting enzyme inhibitors in patients without renal artery stenosis

    Neph Dial Trans

    (1992)
  • M Packer et al.

    Functional renal insufficiency during long-term therapy with captopril and enalapril in severe chronic heart failure

    Ann Int Med

    (1987)
  • EJ Lewis et al.

    The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy

    N Engl J Med

    (1993)
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    Supported by The Medical Foundation Postdoctoral Fellowship Program in Clinical and Community Health Research.

    ☆☆

    Reprint requests: Eric Knight, MD, MPH, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, 221 Longwood Ave, third floor, Boston, MA 02115.

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