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-Chairs
B. Pitt, P. Poole-Wilson
• Data and Safety Monitoring Committee Chair
C. Furberg
• Clinical Endpoint Classification Committee
Chair
L. Frame
• Coordinating Center: Merck Research Labs
Study Director R. 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
Losartan Heart Failure Survival Study
ELITE II
Study Design
60 yrs; NYHA II-IV; EF  40%
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)
Event Driven
(Target 510 Deaths)
~ 2 years
Losartan
50 mg Daily
(N=1578)
Primary Endpoint: All-Cause Mortality
Secondary Endpoint: Sudden Cardiac Death and/or Resuscitated
Arrest
Other Endpoin: All-cause Mortality/Hospitalizations
Safety and Tolerability
Losartan Heart Failure Survival Study ELITE II Baseline Characteristics
Age (mean, yrs)
Gender (male/female %)
Ejection Fraction (mean %)
NYHA Funct. Class II/III/IV (%)
Ischemic History (%)
Prior ACE Inhibitor
Beta Blocker (%)
Diuretic (%)
Cardiac Glycoside (%)
Aspirin/Salicylates (%)
Losartan
Captopril
(N=1578)
(N=1574)
71.4
71.5
70/30
31
49/45/6
80
23
24
77
49
59
69/31
31
49/45/6
79
24
23
78
50
59
p= NS losartan vs captopril
Losartan Heart Failure Survival Study ELITE II Primary Endpoint: All-Cause
Mortality
Probability of Survival
1.0
0.8
0.6
Captopril (N=1574)
Losartan (N=1578)
250 Events
280 Events
0.4
Captopril/Losartan Hazard Ratio (95% C.I.):
0.88 (0.75, 1.05) P=0.16
0.2
0.0
0
100
200
300
400
500
Days of Follow-up
600
700
Losartan Heart Failure Survival Study ELITE II Mortality by Cause
(Adjudicated)
% of Patients
15
10
Losartan (N=1578)
Captopril (N=1574)
5
0
Sudden
Death
Heart
Failure
MI
Stroke
Other CV
Non-CV
Losartan Heart Failure Survival Study ELITE II Mortality by Subgroup
Hazard Ratio of Death
with 95% C.I.
Subgroups at Baseline
Age
 71
 71
Gender
Male
Female
NYHA Class.
III/IV
II
% EF
 32
 32
Beta Blockers
With
Without
Overall
0.4
CaptoprilLosartanHazard
N
N
Ratio
730
844
731
846
0.93
0.84
1083
491
1102
476
0.89
0.87
798
776
801
777
0.93
0.80
783
790
793
785
1.02
0.71
325
1249
354
1224
0.56
0.95
1574
1578
0.88
0.6 0.8 1.0
2.0
Hazard Ratio
Favors Captopril
Favors Losartan
Losartan Heart Failure Survival Study - ELITE II
Secondary Endpoint: Sudden Death / Resuscitated
Arrest
Event-Free Probability
1.0
0.8
0.6
Captopril (N=1574)
Losartan (N=1578)
115 Events
142 Events
0.4
0.2
0.0
0
Captopril/Losartan Hazard Ratio (95% C.I.):
0.80 (0.63, 1.03) P=0.08
100
200
300
400
500
Days of Follow-up
600
700
Losartan Heart Failure Survival Study ELITE II Hospitalization By Cause
(Adjudicated)
% of Patients
30
20
Losartan (N=1578)
Captopril (N=1574)
10
#
0
Heart
Failure
MI
CAD
Stroke/TIA
p=NS between groups
# CAD includes angina, unstable angina, revascularization, etc
Resusc
Arrest
Non-CV
Losartan Heart Failure Survival Study - ELITE II
Tertiary Endpoint: All-Cause Mortality /
Hospitalization
Event-Free Probability
1.0
Captopril/Losartan Hazard Ratio (95% C.I.):
0.94 (0.85, 1.04) P=0.21
0.8
0.6
0.4
Captopril (N=1574)
Losartan (N=1578)
707 Events
752 Events
0.2
0.0
0
100
200
300
400
500
Days of Follow-up
600
700
Losartan Heart Failure Survival Study - ELITE II
Withdrawal for Adverse Experience (Excluding
Death)
% of Patients
20
15
**
Losartan (N=1578)
Captopril (N=1574)
10
**
5
**
0
Any AE
Drug-Related
AE
Cough
** p0.001 between groups
HF
Losartan Heart Failure Survival Study ELITE II Study Endpoint Summary
Crude Rate
Adjusted
Hazards
Ratio (95%
CI)
Captopril
(N=1574)
Losartan
(N=1578)
Primary Endpoint:
All-cause
Mortality
250 (15.9%)
280 (17.7%)
0.88 (0.75, 1.05)
0.16
Secondary Endpoint:
Sudden Death/
Resusc. Arrest
115 (7.3%)
142 (9.0%)
0.80 (0.63, 1.03)
0.08
Tertiary Endpoints:
All-cause Mortality/
Hospitalization
707 (44.9%)
752 (47.7%)
0.94 (0.85, 1.04)
0.21
Withdrawal for
228 (14.5%)
Adverse Experience
149 (9.4%)
P-Value
<0.001