SOLVD: Studies Of Left Ventricular Dysfunction
Purpose
To determine whether long-term therapy with the ACE inhibitor enalapril can reduce mortality and hospitalization for heart failure in patients with clinically stable chronic congestive heart failure (CHF) and decreased ejection fraction
Reference
The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991;325:293–302.
SOLVD: Studies Of Left Ventricular Dysfunction - TRIAL DESIGN -
Design
Multicenter, multinational, randomized, double-blind, placebo-controlled
Patients
2569 clinically stable patients with chronic CHF and ejection fraction <0.35, approximately 90% in NYHA classes II and III; patients with MI in previous month excluded
Follow up and primary endpoint
Average 41.4 months follow up. Primary endpoints mortality and hospitalization for worsening heart failure
Treatment
Patients assigned enalapril received 2.5 or 5 mg twice daily initially, then 2.5–20 mg per day
SOLVD: Studies Of Left Ventricular Dysfunction - RESULTS -
All-cause mortality and death or hospitalization due to heart failure significantly reduced in enalapril group compared with placebo
Significant reduction in several categories of death due to cardiovascular causes, majority attributable to reduction in progressive heart failure
Benefit in terms of death or hospitalization due to heart failure significantly smaller for highest tertile baseline ejection fraction
No significant difference in MI in placebo and enalapril groups
Most common side effects hypotension and increased serum creatinine
SOLVD: Studies Of Left Ventricular Dysfunction - RESULTS continued -
Months after start of treatment
Mortality
(%)
0
0
6
12
18
36
1284
1285
Placebo
Enalapril
No. of
patients alive
1159
1195
1085
1127
1005
1069
939
1010
819
891
669
697
487
526
299
333
24
30
42
48
20
10
40
30
50
Cumulative all-cause mortality
P = 0.0036
Placebo
Enalapril
The SOLVD Investigators.
N Engl J Med
1991;
325
:293–302.
SOLVD: Studies Of Left Ventricular Dysfunction - RESULTS continued -
Placebo
n=1284
(%)
One-sided
P
Death and hospitalization for CHF
The SOLVD Investigators.
N Engl J Med
1991;
325
:293–302.
Enalapril
n=1285
(%)
reduction
(95% CI)
Death due to any cause
Death or hospitalization for CHF
Cardiovascular death
a
Cardiac death
Arrhythmia without worsening CHF
Heart failure or arrhythmia with CHF
39.7
57.3
35.9
34.3
8.8
19.5
35.2
47.7
31.1
29.3
8.2
16.3
16 (5
–26)
26 (18
–34)
18 (6
–28)
19 (7
–29)
10 (-17
–31)
22 (6
–35)
<0.0036
<0.0001
<0.002
<0.0015
–
<0.0045
a
Cardiac causes (including MI), stroke and other vascular causes
% Risk
SOLVD: Studies Of Left Ventricular Dysfunction - RESULTS continued -
Effect of enalapril on ejection fraction subgroups (% of patients)
Ejection fraction (%)
Overall
Ejection fraction (%)
6–22
23–29
30–35
Overall
50
39
28
40
69
56
45
57
41
33
31
35
52
47
44
48
24
24
-7
16
35
30
12
26
The SOLVD Investigators.
N Engl J Med
1991;
325
:293–302.
50
0
%RR
-50
Death
Death or
hospitalization
Placebo
n=1284
Enalapril
n=1285
RR
(%)
50
0
-50
SOLVD: Studies Of Left Ventricular Dysfunction - SUMMARY -
In patients with clinically stable chronic CHF and decreased ejection fraction (<0.35), long-term enalapril:
Reduced death due to all causes and death or hospitalization due to heart failure
Had greatest effect in reducing death due to progressive heart failure
Conferred more benefit in patients in lower two tertiles for ejection fraction (6–29%)
Did not reduce MI