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Published at www.nejm.org November 11, 2008 (10.1056/NEJMoa0805450)

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ABSTRACT

Background Approximately 50% of patients with heart failure have a left ventricular ejection fraction of at least 45%, but no therapies have been shown to improve the outcome of these patients. Therefore, we studied the effects of irbesartan in patients with this syndrome.

Methods We enrolled 4128 patients who were at least 60 years of age and had New York Heart Association class II, III, or IV heart failure and an ejection fraction of at least 45% and randomly assigned them to receive 300 mg of irbesartan or placebo per day. The primary composite outcome was death from any cause or hospitalization for a cardiovascular cause (heart failure, myocardial infarction, unstable angina, arrhythmia, or stroke). Secondary outcomes included death from heart failure or hospitalization for heart failure, death from any cause and from cardiovascular causes, and quality of life.

Results During a mean follow-up of 49.5 months, the primary outcome occurred in 742 patients in the irbesartan group and 763 in the placebo group. Primary event rates in the irbesartan and placebo groups were 100.4 and 105.4 per 1000 patient-years, respectively (hazard ratio, 0.95; 95% confidence interval [CI], 0.86 to 1.05; P=0.35). Overall rates of death were 52.6 and 52.3 per 1000 patient-years, respectively (hazard ratio, 1.00; 95% CI, 0.88 to 1.14; P=0.98). Rates of hospitalization for cardiovascular causes that contributed to the primary outcome were 70.6 and 74.3 per 1000 patient-years, respectively (hazard ratio, 0.95; 95% CI, 0.85 to 1.08; P=0.44). There were no significant differences in the other prespecified outcomes.

Conclusions Irbesartan did not improve the outcomes of patients with heart failure and a preserved left ventricular ejection fraction. (ClinicalTrials.gov number, NCT00095238 [ClinicalTrials.gov] .)

Source Information

From the University of California, San Francisco, and San Francisco Veterans Affairs Medical Center, San Francisco (B.M.M.); Georgetown University and Washington DC Veterans Affairs Medical Center, Washington, DC (P.E.C.); British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (J.J.M.); Université Paris 6 and Hospital Pitié–Salpêtrière, Paris (M.K.); Hamilton Health Sciences, McMaster University, Hamilton, ON, Canada (R.M.); Ralph H. Johnson Veterans Affairs Medical Center and Medical University of South Carolina, Charleston (M.R.Z.); University of Wisconsin, Madison (S.A., E.I.); Bristol-Myers Squibb, Princeton, NJ (M.D., A.P.); and Sanofi-Aventis, Bridgewater, NJ (C.S.).

This article (10.1056/NEJMoa0805450) was published at www.nejm.org on November 11, 2008. It will appear in the December 4 issue of the Journal.

Address reprint requests to Dr. Massie at the Veterans Affairs Medical Center, 111C, 4150 Clement St., San Francisco, CA 94121, or at barry.massie{at}va.gov.

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