CONSENSUS: Cooperative North Scandinavian Enalapril Survival Study

1
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 316142935.

2
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 gt600 (men)
  or gt500 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

3
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, P0.003)
• 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,
  Plt0.001)
• Withdrawal due to hypotension higher in enalapril
  group, but overall withdrawal rate similar in the
  two groups

4
CONSENSUS Cooperative North Scandinavian
Enalapril Survival Study- RESULTS continued -
Cumulative probability of death
Probability
0.8
0.6
0.4
0.2
Placebo
Enalapril
0.0
0
2
4
6
8
10
12
Months after randomization
126
78
59
47
34
24
17
Placebo
127
98
82
73
59
42
26
Enalapril
CONSENSUS Trial Study Group. N Engl J Med
1987316142935.
5
CONSENSUS Cooperative North Scandinavian
Enalapril Survival Study- RESULTS continued -

All-cause mortality
Placebo
Enalapril
Reduction in
P
(n126)
(n127)
relative risk
No. ()
No. ()
()
40
Mortality at 6 months
55
0.002
(44)
33
(26)

(180 days)





31
Mortality at 1 year
66
0.001
(52)
46
(36)

(360 days)





27
Total mortality
68
0.003
(54)
50
(39)
CONSENSUS Trial Study Group. N Engl J Med
1987316142935.
6
CONSENSUS Cooperative North Scandinavian
Enalapril Survival Study- RESULTS continued -

Cardiac causes of death
No. of deaths
Placebo
Enalapril
P
(n126)
(n127)
Cardiac death within 24 h of
19
20
gt0.25
new symptoms



Sudden cardiac death
14
14
gt0.25
(within 1 h of new symptoms)



Progression of congestive heart failure
44
22
0.001
Other cardiac death
1
2
CONSENSUS Trial Study Group. N Engl J Med
1987316142935.
7
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