ArticlesRandomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE)*
Introduction
Angiotensin-converting-enzyme (ACE) inhibitors reduce morbidity and mortality in patients with chronic heart failure and systolic left-ventricular dysfunction as well as in patients who have had a myocardial infarction.1, 2, 3, 4, 5, 6, 7, 8, 9 The benefits of ACE inhibitors have been mostly attributed to blockade of angiotensin II production and/or to a decrease in the breakdown of bradykinin.10, 11 Bradykinin has been shown to have beneficial effects associated with the release of nitric oxide and prostacyclin, which may contribute to the haemodynamic effects of ACE inhibition. Bradykinin may, however, also be responsible for some of the adverse reactions to ACE inhibitors such as cough, angio-oedema, renal dysfunction, and hypotension,10, 11, 12, 13, 14 and these sideeffects may explain in part why ACE inhibitors are used in less than 30% of patients with heart failure despite the proven clinical benefit of these agents.15
Orally active, non-peptide angiotensin II type 1 receptor antagonists such as losartan can block this receptor specifically without increasing bradykinin levels,16 and since angiotensin II may be produced by alternate pathways17, 18, 19, 20 such drugs may have additional advantages over ACE inhibitors where blockade of the effects of angiotensin II is incomplete. Losartan is licenced for the treatment of hypertension in many countries, and in earlier studies in patients with symptomatic heart failure, oral losartan produced beneficial haemodynamic effects both acutely and with chronic dosing.21, 22
The Evaluation of Losartan in the Elderly (ELITE) study has compared effects on renal function, morbidity/mortality, and tolerability of long-term treatment with losartan or captopril in patients aged 65 years and older with symptomatic heart failure. The primary endpoint was the tolerability measure of a persisting increase in serum creatinine of 0·3 mg/dL (26·5 μmol/L) or more on therapy; the secondary endpoint was the composite efficacy measure of death and/or hospital admissions for heart failure. Other prespecified efficacy measures included total mortality and hospital admission for heart failure separately, New York Heart Association (NYHA) functional class, and admission to hospital for myocardial infarction or unstable angina.
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Patients and methods
The ELITE study10 was a prospective double-blind, randomised, parallel, captopril-controlled clinical trial conducted at 125 centres in the United States, Europe and South America. The study was approved by institutional review boards at each site; all patients gave written informed consent. An independent Data and Safety Monitoring Committee monitored the progress of the study.
Results
Recruitment began in May, 1994; the last patient was enrolled in July, 1995; and follow-up was completed in June, 1996. Enrolment of patients at the 125 participating centres ranged from 1 to 93 (median of 4); recruitment proved difficult and a substantial number of sites were required to achieve the study sample. Of the 722 patients enrolled, 352 were randomised to losartan and 370 to captopril (figure 1). The two treatment groups were similar with respect to all baseline characteristics (
Discussion
ELITE is the first long-term (48 weeks) study comparing an angiotensin II type 1 receptor antagonist with an ACE inhibitor in patients with symptomatic heart failure and systolic left-ventricular dysfunction. Captopril was chosen as the comparison ACE inhibitor drug because it may have fewer renal effects than longer-acting ACE inhibitors.24 The incidence of persistent renal dysfunction was not different between the losartan and captopril groups (both 10·5%), and fewer than 2% of patients
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Investigators listed at end of paper