Losartan Heart Failure Survival Study ELITE II Losartan Heart Failure Survival Study ELITE II A Multicenter, Double-Blind, Randomized, Parallel, Captopril-Controlled.

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Presentation transcript:

Losartan Heart Failure Survival Study ELITE II Losartan Heart Failure Survival Study ELITE II A Multicenter, Double-Blind, Randomized, Parallel, Captopril-Controlled Study to Evaluate the Effects of Losartan on Mortality in Patients with Symptomatic Heart Failure 46 Countries; 289 Sites; 3152 Patients Steering Committee Co-ChairsB. Pitt, P. Poole-Wilson Steering Committee Co-ChairsB. Pitt, P. Poole-Wilson Data and Safety Monitoring Committee ChairC. Furberg Data and Safety Monitoring Committee ChairC. Furberg Clinical Endpoint Classification CommitteeChairL. Frame Clinical Endpoint Classification CommitteeChairL. Frame Coordinating Center: Merck Research LabsStudy DirectorR. Segal Coordinating Center: Merck Research LabsStudy DirectorR. Segal

Losartan Heart Failure Survival Study ELITE II Primary Hypothesis: Treatment with losartan will reduce all-cause mortality compared to captopril Power: 90% to detect a 25% difference [p=0.043] intention-to-treat Secondary Hypothesis: Treatment with losartan will reduce the incidence of sudden death and/or resuscitated arrest compared to captopril Other Endpoints: All-cause mortality/hospitalizations Safety and tolerability

Study Design Losartan Heart Failure Survival Study ELITE II 60 yrs; NYHA II-IV; EF 40%  60 yrs; NYHA II-IV; EF  40% ACE-I/AIIA naive or <7 days in 3 months prior to entry ACE-I/AIIA naive or <7 days in 3 months prior to entry Standard Rx (± Dig/Diuretics), ß-blocker stratification Captopril 50 mg 3 times daily (N=1574) Primary Endpoint: All-Cause Mortality Secondary Endpoint: Sudden Cardiac Death and/or Resuscitated Arrest Other Endpoin: All-cause Mortality/Hospitalizations Safety and Tolerability Safety and Tolerability Event Driven (Target 510 Deaths) ~ 2 years Losartan 50 mg Daily (N=1578)

Age (mean, yrs) Gender (male/female %) 70/30 69/31 Ejection Fraction (mean %) NYHA Funct. Class II/III/IV (%) 49/45/6 49/45/6 Ischemic History (%) Prior ACE Inhibitor Beta Blocker (%) Diuretic (%) Cardiac Glycoside (%) Aspirin/Salicylates (%) Losartan (N=1578)Captopril(N=1574) p= NS losartan vs captopril Losartan Heart Failure Survival Study - ELITE II Baseline Characteristics

Losartan Heart Failure Survival Study - ELITE II Primary Endpoint: All-Cause Mortality Days of Follow-up Probability of Survival Losartan (N=1578)280 Events Captopril(N=1574) 250 Events Captopril/Losartan Hazard Ratio (95% C.I.): 0.88 (0.75, 1.05) P=0.16

Losartan Heart Failure Survival Study - ELITE II Mortality by Cause (Adjudicated)

Losartan Heart Failure Survival Study - ELITE II Mortality by Subgroup Hazard Ratio Age Gender NYHA Class. % EF Beta Blockers Overall  71  71 Male Female III/IV II  32  32 With Without NN Hazard Ratio LosartanCaptopril Hazard Ratio of Death with 95% C.I.Subgroups at Baseline Favors CaptoprilFavors Losartan

Losartan Heart Failure Survival Study - ELITE II Secondary Endpoint: Sudden Death / Resuscitated Arrest Days of Follow-up Event-Free Probability Losartan (N=1578)142 Events Captopril(N=1574) 115 Events Captopril/Losartan Hazard Ratio (95% C.I.): 0.80 (0.63, 1.03) P=0.08

Losartan Heart Failure Survival Study - ELITE II Hospitalization By Cause (Adjudicated) p=NS between groups # # CAD includes angina, unstable angina, revascularization, etc

Losartan Heart Failure Survival Study - ELITE II Tertiary Endpoint: All-Cause Mortality / Hospitalization Days of Follow-up Event-Free Probability Losartan (N=1578)752 Events Captopril(N=1574) 707 Events Captopril/Losartan Hazard Ratio (95% C.I.): 0.94 (0.85, 1.04) P=0.21

Losartan Heart Failure Survival Study - ELITE II Withdrawal for Adverse Experience (Excluding Death) ** ** p  between groups **

Losartan Heart Failure Survival Study - ELITE II Study Endpoint Summary Crude Rate Losartan (N=1578) Captopril (N=1574) Adjusted Hazards Ratio (95%CI) All-cause Mortality 280 (17.7%)250 (15.9%) 0.88 (0.75, 1.05) All-cause Mortality/ Hospitalization 752 (47.7%)707 (44.9%) 0.94 (0.85, 1.04) Sudden Death/ Resusc. Arrest 142 (9.0%)115 (7.3%) 0.80 (0.63, 1.03) Primary Endpoint: Secondary Endpoint: Tertiary Endpoints: P-Value Withdrawal for Adverse Experience 149 (9.4%)228 (14.5%) <0.001