A multinational study has shown no significant difference between losartan (Cozaar, an angiotensin-II receptor antagonist) and captopril (an ACE inhibitor) in reducing mortality in patients with heart failure. The results were announced on November 10 at the American Heart Association meeting in Atlanta, US.
The study, called ELITE II (evaluation of losartan in the elderly), was carried out after unexpected findings from an earlier, smaller study (ELITE), in which losartan was associated with a lower mortality than captopril (PJ, March 29, 1997, p432). The ELITE study was not set up to assess mortality differences. ELITE II was specifically designed to assess the difference between the two classes in reducing deaths.
The double-blind, parallel-group study involved 3,152 elderly patients from 289 medical centres in 46 countries. Patients were randomised to treatment with losartan (titrated to 25mg or 50mg daily as tolerated) or captopril (titrated as tolerated to 50mg three times a day). All patients were over 60 years of age with symptomatic heart failure and left ventricular ejection fraction of 40 per cent or less.
During the two-year trial, 250 of the 1,574 patients in the captopril group died (15.9 per cent), compared with 280 of the 1,578 patients (17.7 per cent) treated with losartan; 7.3 per cent of the captopril group and 9 per cent of the losartan group experienced sudden cardiac death and/or resuscitated cardiac arrest. No statistically significant difference between the two drugs was shown.
Preliminary findings suggested that losartan was better tolerated, with fewer side effects and a lower rate of patient discontinuation than captopril.
Speaking in Atlanta, Professor Philip Poole-Wilson (professor of cardiology, Imperial College school of medicine, University of London) suggested that, because wider experience had been gained with ACE inhibitors, the trial steering committee believed that this class should remain first choice for treating heart failure. He added: "If an ACE inhibitor cannot be used for whatever reason, I think that there is a reasonable medical view that it would be appropriate to consider losartan as a treatment in those patients."
Losartan is not licensed for heart failure in the UK. Merck Sharp & Dohme says that it is waiting for the full trial data before deciding whether or not to apply for a licence. However, the company has announced that, based on the ELITE II results, it will not seek regulatory approval for Cozaar in heart failure in the United States, and that it will request removal of the first-line indication in any country where Cozaar is approved for this use in heart failure.