Transcript SOLVD - Clinical Trial Results

SOLVD
(Studies of Left Ventricular Dysfunction)
• Enalapril vs placebo in 6,794 patients
• Ejection fraction < 35%
• End points include:
– Delaying the progression of heart failure
– Improving signs and symptoms
– Reducing mortality
• Treatment arm - 2,568 symptomatic class II-III patients most
on digitalis and diuretics
• Prevention arm - 4,226 asymptomatic class I-II patients,
most on no concomitant therapy
N Engl J Med 1991:325:293-302
SOLVD Treatment Trial
All Cause Mortality
50
Placebo
Enalapril
Mortality%
40
16% Risk Reduction
p = 0.0036
30
20
10
0
0
6
12
18
24
Months
N Engl J Med 1991;325:293-302
30
36
42
48
Benefits of Enalapril
• Patients: Symptomatic HF patients with LVD (EF < 35%)
• Increased Survival
–
–
–
–
–
–
32% at 3 months
28% at 6 months
21% at 12 months
18% at 24 months
12% at 36 months
12% at 48 months
• 11% reduction of overall mortality at end of study (P=0.0036)
The SOLVD Investigators, N Engl J Med. 1991;325:293
SOLVD Treatment Trial
Mortality or Hospitalization for CHF
70
Placebo
Enalapril
Events %
60
50
40
30
26% Risk Reduction
p<0.0001
20
10
0
0
6
12
18
24
Months
N Engl J Med 1991;325:293-302
30
36
42
48
SOLVD Treatment-Enalapril
Symptomatic HF Patients with LVD (EF < 35%)
(NYHA Class II-III)
30% Reduction
p<0.001
1000
800
600
Placebo + Conv TX
Enalapril + Conv TX
400
200
0
971
683
Number of Hospitalizations Due to Heart failure
The SOLVD Investigators, N Engl J Med, 1991
SOLVD Treatment-Enalapril
Symptomatic HF Patients with LVD (EF < 35%)
(NYHA Class II-III)
33% Reduction
p<0.001
250
200
150
Placebo + Conv TX
Enalapril + Conv TX
100
50
0
234
157
Number of Readmissions for Heart failure
The SOLVD Investigators, N Engl J Med, 1991
SOLVD Treatment Trial
• Implications:
– Treating 1,000 patients for 3 years
• Prevents about 50 deaths
• Prevents about 350 hospitalizations
Benefits of Enalapril
• Patients: Symptomatic HF patients with LVD (EF < 35%)
• Decreased hospitalizations
– 48% at 3 months
– 51% at 6 months
– 46% at 12 months
– 23% at 24 months
– 28% at 36 months
• 30% reduction of overall hospitalization at end of study
(P<0.0001)
• Convenient once - or twice - daily dosing
The SOLVD Investigators, N Engl J Med. 1991;325:293
SOLVD Treatment Trial
Conclusions
• Hospitalizations:
– Risk reduced by 20% (p<0.001)
– Significant reduction in CHF
hospitalization by 1/3 (p<0.0001)
– Sustained benefit over 4 years
N Engl J Med 1991;325:293-302
Mortality from All Causes (%)
SOLVD Prevention Trial
All Cause Mortality
25
Placebo
Enalapril
20
Risk Reduction 8%
15
10
P=0.30
5
0
0
6
12
18
24
Months
30
36
42
48
N Engl J Med 1992;327:685-91
% Events
SOLVD Prevention Trial
Death or Development of CHF
50
45
40
35
30
25
20
15
10
5
0
Placebo
Enalapril
Risk Reduction 29%
p<0.001
0
6
12
18
24
30
36
Months of Follow-up
42
48
N Engl J Med 1992;327:685-91
% Events
SOLVD Prevention Trial
First Hospitalization for CHF
18
16
14
12
10
8
6
4
2
0
Placebo
Enalapril
Risk Reduction 36%
p<0.001
0
6
12
18
24
30
36
42
48
Months of Follow-up
N Engl J Med 1992;327:685-91
SOLVD Prevention Trial
35
27.8
30
25
placebo
enalapril
22.3
20
months
15
13.2
8.3
10
5
0
Median length of time to first CHF
hospitalization
Median length of time to develop CHF
N Engl J Med 1992;327:685-91
SOLVD Prevention- Enalapril
Asymptomatic HF Patients w/ LVD (EF < 35%)
(NYHA Class I-II)
32% Fewer First
Hospitalizations
p<0.001
300
250
200
Placebo (n=2,177)
Enalapril (n=2,111)
150
100
50
0
273
184
Number of First Hospitalizations for Heart Failure
The SOLVD Investigators, N Engl J Med, 1992.
SOLVD Prevention Trial
Morbidity and Combined Outcomes
Endpoint
Placebo
%
Enalapril
%
RR
P value
Development of CHF
30.2
20.7
37%
<0.001
Development of CHF and
anti-CHF Rx
First Hospitalization for CHF
22.5
13.9
43%
<0.001
12.9
8.7
36%
<0.001
Multiple Hospitalization for
CHF
Death or Development of
CHF
Death or Hospitalization for
CHF
4.8
2.7
44%
<0.001
38.6
29.8
29%
<0.001
24.5
20.6
20%
<0.001
Enalapril - Dosing
Initial dose:
enalapril
2.5 mg bid
Targeted dose:
enalapril
20 mg
Mean daily dose:
CONSENSUS 18.4 mg
SOLVD-T
16.6 mg
V-HeFT II
15 mg
In the SOLVD Treatment Trial dosage ranged
from 2.5 mg to 10 mg twice daily
Careful dose titration is important to minimize risk
of hypotension in heart failure patients