Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: Randomised trial - The Losartan Heart Failure Survival Study ELITE II

Background. The ELITE study showed an association between the angiotensin II antagonist losartan and an unexpected survival benefit in elderly heart-failure patients, compared with captopril, an angiotensin-converting-enzyme (ACE) inhibitor. We did the ELITE II Losartan Heart Failure Survival Study to confirm whether losartan is superior to captopril in improving survival and is better tolerated. Methods. We undertook a double-blind, randomised, controlled trial of 3152 patients aged 60 years or older with New York Heart Association class II-IV heart failure and ejection fraction of 40% or less. Patients, stratified for β-blocker use, were randomly assigned losartan (n = 1578) titrated to 50 mg once daily or captopril (n = 1574) titrated to 50 mg three times daily. The primary and secondary endpoints were all-cause mortality, and sudden death or resuscitated arrest. We assessed safety and tolerability. Analysis was by intention to treat. Findings. Median follow-up was 555 days. There were no significant differences in all-cause mortality (11.7 vs 10.4% average annual mortality rate) or sudden death or resuscitated arrests (9.0 vs 7.3%) between the two treatment groups (hazard ratios 1.13 [95.7% CI 0.95-1.35], p = 0.16 and 1.25 [95% CI 0.98-1.60], p = 0.08). Significantly fewer patients in the losartan group (excluding those who died) discontinued study treatment because of adverse effects (9.7 vs 14.7%, p < 0.001), including cough (0.3 vs 2.7%). Interpretation. Losartan was not superior to captopril in improving survival in elderly heart-failure patients, but was significantly better tolerated. We believe that ACE inhibitors should be the initial treatment for heart failure, although angiotensin II receptor antagonists may be useful to block the renin angiotensin aldosterone system when ACE inhibitors are not tolerated.