SOLVD: Studies Of Left Ventricular Dysfunction

1
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 1991325293302.

2
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 lt0.35, 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 2.520 mg per day

3
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

4
SOLVD Studies Of Left Ventricular Dysfunction-
RESULTS continued -

Cumulative all-cause mortality
Mortality
50
()
40
30
20
10
Placebo
P 0.0036
Enalapril
0
0
6
12
18
36
24
30
42
48
Months after start of treatment
No. of
patients alive
1284
Placebo
1159
1085
1005
939
819
669
487
299
1285
Enalapril
1195
1127
1069
1010
891
697
526
333
The SOLVD Investigators.
N Engl J Med
1991
325
293302.
5
SOLVD Studies Of Left Ventricular Dysfunction-
RESULTS continued -

Death and hospitalization for CHF
Placebo
Enalapril
Risk
One-sided
n1284
n1285
reduction
P
()
()
(95 CI)
Death due to any cause
39.7
35.2
16 (5
26)
lt0.0036
Death or hospitalization for CHF
57.3
47.7
26 (18
34)
lt0.0001
a
Cardiovascular death
35.9
31.1
18 (6
28)
lt0.002
Cardiac death
34.3
29.3
19 (7
29)
lt0.0015
Arrhythmia without worsening CHF
8.8
8.2
10 (-17
31)

Heart failure or arrhythmia with CHF
19.5
16.3
22 (6
35)
lt0.0045
a
Cardiac causes (including MI), stroke and other
vascular causes
The SOLVD Investigators.
N Engl J Med
1991
325
293302.
6
SOLVD Studies Of Left Ventricular Dysfunction -
RESULTS continued -

Effect of enalapril on ejection fraction
subgroups ( of patients)
Placebo
Enalapril
RR
n1284
n1285
()
Ejection fraction ()
50
41
24
39
33
24
Death
28
31
-7
Overall
40
35
16
50
0
-50
Ejection fraction ()
622
69
52
35
Death or
2329
56
47
30
hospitalization
3035
45
44
12
Overall
57
48
26
-50
50
0
The SOLVD Investigators.
N Engl J Med
1991
325
293302.
RR
7
SOLVD Studies Of Left Ventricular Dysfunction-
SUMMARY -

• In patients with clinically stable chronic CHF
  and decreased ejection fraction (lt0.35),
  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 (629)
• Did not reduce MI