CONSENSUS: Cooperative North Scandinavian Enalapril Survival Study
Purpose
To determine whether the ACE inhibitor enalapril reduces mortality in patients with severe congestive heart failure
Reference
The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987; 316:1429–35.
CONSENSUS: Cooperative North Scandinavian Enalapril Survival Study - TRIAL DESIGN -
Design
Multicenter, multinational, randomized, double-blind, placebo-controlled
Patients
253 patients with severe congestive heart failure (NYHA class IV) and heart size >600 (men) or >500 mL/m2 (women), and receiving a diuretic and digoxin; patients with MI in previous 2 months excluded
Follow up and primary endpoint
Primary endpoint: all-cause mortality. Mean 188 days follow up
Treatment
Placebo or enalapril initiated at 5 mg twice daily; increased to 10 mg twice daily after 1 week if no side effects, then to maximum 20 mg twice daily according to clinical response
CONSENSUS: Cooperative North Scandinavian Enalapril Survival Study - RESULTS -
Trial halted early on recommendation of Ethical Review Committee because of evident benefit of enalapril
Significant reduction in all-cause mortality in enalapril group at 6 months and 1 year, with overall relative risk reduction of 27% (39 vs. 54%, P=0.003)
Reduction in mortality entirely attributed to reduction in death due to progression of heart failure
No difference in incidence of sudden cardiac death within the two groups
NYHA class improved in significantly higher proportion of enalapril group (42 vs. 22%, P<0.001)
Withdrawal due to hypotension higher in enalapril group, but overall withdrawal rate similar in the two groups
CONSENSUS: Cooperative North Scandinavian Enalapril Survival Study - RESULTS continued -
Months after randomization
Probability
0
2
4
126
127
78
98
59
82
47
73
34
59
24
42
17
26
Placebo:
Enalapril:
6
8
10
12
0.2
0.0
0.6
0.4
0.8
Cumulative probability of death
Placebo
Enalapril
CONSENSUS Trial Study Group. N Engl J Med 1987;316:1429–35.
CONSENSUS: Cooperative North Scandinavian Enalapril Survival Study - RESULTS continued -
P
Mortality at 6 months
(180 days)
Mortality at 1 year
(360 days)
Total mortality
55
66
68
40
31
27
0.002
0.001
0.003
All-cause mortality
Placebo
(n=126)
No. (%)
Enalapril
(n=127)
No. (%)
CONSENSUS Trial Study Group. N Engl J Med 1987;316:1429–35.
(44)
(52)
(54)
33
46
50
(26)
(36)
(39)
Reduction in
relative risk
(%)
CONSENSUS: Cooperative North Scandinavian Enalapril Survival Study - RESULTS continued -
P
Cardiac death within 24 h of
new symptoms
Sudden cardiac death
(within 1 h of new symptoms)
Progression of congestive heart failure
Other cardiac death
19
14
44
1
Cardiac causes of death
Placebo
(n=126)
Enalapril
(n=127)
CONSENSUS Trial Study Group. N Engl J Med 1987;316:1429–35.
20
14
22
2
>0.25
>0.25
0.001
No. of deaths
CONSENSUS: Cooperative North Scandinavian Enalapril Survival Study - SUMMARY -
In patients with severe congestive heart failure and increased heart size, enalapril:
Reduced all-cause mortality
Reduced death due to progression of heart failure
Did not change incidence of sudden cardiac death