ELITE II (evaluation of losartan in the elderly)

ELITE II (Evaluation of Losartan in the Elderly)Presenters: Bertram Pitt, University of Michigan, Ann Arbor,Mich; Philip Poole-Wilson, National Heart & Lung Institute,London, England, UK.The study: A large-scale multicenter (289 clinical sites in46 countries) randomized, controlled trial of Losartan (anangiotensin receptor blocker) in patients with heart failure. Atotal of 3152 patients with class II to IV heart failure and anEF #40% were randomized to captopril (50 mg TID,n51574) or Losartan (50 mg/d, n51578). To qualify for thestudy, patients could not have been on prior ACE inhibitortherapy for $7 days. Patients were subsequently followed fora mean of 558 days. The primary endpoint of the study wasall-cause mortality.The results: There was no significant difference in all-cause mortality in the 2 groups (captopril 15.9%; losartan17.7%). Mortality in both groups was approximately 11%/year. Sudden death tended to be slightly lower (but notsignificantly) in the captopril group. In analyses of variousclinical subsets, patients on b-blockers and patients with anEF.32% showed more benefit with captopril. There werealso no significant differences between group in the compos-ite of sudden death and resuscitated cardiac arrest, in hospi-talization rates, and the composite of all cause mortality andhospitalization. Captopril patients were significantly morelikely to withdraw from therapy (14.5% versus 9.4% withLosartan). Summary: In contrast to the previous ELITE trial, thelarger scale ELITE II trial showed no mortality advantage forthe ARB losartan. ACE-inhibit therapy remains the therapy ofchoice in patients with heart failure. ARBs may be consideredif ACE inhibitors are not tolerated.IMPRESSPresenter: Jean Rouleau, Toronto Hospital, Canada.The study: A multicenter, randomized, controlled trial ofomapatrilat (a novel vasopeptidase inhibitor that blocks bothneutral endopeptidase and angiotensin converting enzyme,and thus enhances the activity of vasodilator peptides (natri-uretic peptides, bradykinin, and adrenomedullin) and reducesangiotensin II levels in patients with A total of 573 patientswith class II to IV CHF were randomized to 24 weeks oftherapy with omapatrilat (target dose 40 mg qd) or lisinopril(target dose 20 mg qd). All patients were on ACE inhibitorsbefore randomization. The primary endpoint of the study wasa composite of mortality and morbidity (hospitalization forworsening heart failure or study drug discontinuation). The results: Exercise time at 12 weeks was slightlyprolonged in both groups. Omapatrilat patients with class IIIheart failure showed significantly more improvement in NewYork Heart Association CHF class (39 improved, 0 worsenedversus 29 improved, 4 worsened with lisinopril). Omapatrilatpatients showed significant improvement in the morbidity/mortality composite endpoint (16% versus 29% with lisino-pril; P,0.04). Both drugs appeared well tolerated, althoughomapatrilat was associated with a lower overall incidence ofserious adverse events and elevations of BUN/creatinine.Summary: In patients with symptomatic CHF, the vasopep-tidase inhibitor omapatrilat was associated with improvedsymptoms and morbidity/mortality in comparison with lisi-nopril. Larger scale confirmatory efficacy trials arewarranted.BEST (Beta Blocker Evaluation of Survival Study)Presenters: Michael Domanski, National Heart, Lung, andBlood Institute, Bethesda, Md; Eric Eichhorn, University ofTexas-Southwestern, Dallas, Tex.The study: A multicenter, randomized, placebo-controlledtrial of bucindolol (a nonselective B