COPERNICUS: Carvedilol Prospective Randomized Cumulative Survival trial
Purpose
To assess the effect of carvedilol, a β1-, β2- and α1-receptor blocker, on mortality in patients with severe chronic heart failure
Reference
Packer M, Coats AJS, Fowler M et al. for the COPERNICUS Study Group. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001;344:1651–8.
COPERNICUS: Carvedilol Prospective Randomized Cumulative Survival trial - TRIAL DESIGN -
Design
Multicenter, multinational, randomized, double-blind, placebo-controlled
Patients
2289 patients with symptoms of heart failure at rest or on minimal exertion and left ventricular ejection fraction <25%, receiving standard therapy (diuretic plus ACE inhibitor/angiotensin II-receptor antagonist)
Follow up and primary end point
Mean 10.4 months follow up. Primary endpoint all-cause mortality
Treatment
Placebo or carvedilol 3.125 mg twice daily for 2 weeks, increased stepwise over several weeks as tolerated to target dose 25 mg twice daily
COPERNICUS: Carvedilol Prospective Randomized Cumulative Survival trial - RESULTS -
Study halted early on recommendation of data and safety monitoring board because beneficial effect of carvedilol exceeded prespecified interim monitoring boundaries
Significant reduction in all-cause mortality in carvedilol group (130 deaths vs. 190 in placebo group, 35% relative risk reduction, P=0.0014), equating to 11.4% cumulative risk of death at 1 year vs. 18.4% with placebo
Significant reduction in combined endpoint of death or hospitalization for any reason (425 vs. 507, 24% relative RR, P<0.001)
These beneficial effects seen in all subgroups examined, including patients at highest risk
Permanent discontinuation of treatment 23% lower in carvedilol group than placebo group at 1 year (14.8 vs. 18.5%, P=0.02)
COPERNICUS: Carvedilol Prospective Randomized Cumulative Survival trial - RESULTS continued -
Months
0
3
6
9
18
15
12
21
50
80
70
60
90
100
Survival (%)
Months
0
3
6
9
18
15
12
21
0
60
40
20
80
100
Event-free survival (%)
All-cause mortality and hospitalization for any reason
Packer et al.
N Engl J Med
2001;
344
:1651
–
8.
35% relative risk reduction
(95% CI 19
–
48%)
P=0.00013
P=0.0014 adjusted for
interim analysis
24% relative risk reduction
(95% CI 13
–
33%)
P<0.001
Placebo
Carvedilol
COPERNICUS: Carvedilol Prospective Randomized Cumulative Survival trial - RESULTS continued -
0.0
0.5
1.0
Subgroup analysis
1.5
Packer et al.
N Engl J Med
2001;
344
:1651
–
8.
Male
Female
<65 years old
>
65 years old
North or South America
Other continents
LVEF <0.20
LVEF
>
0.20
Ischemic
Non-ischemic
No recent hospitalization
Recent hospitalization
All patients
0.0
0.5
1.0
1.5
Hazard ratio
(and 95% CI)
Favors
carvedilol
Favors
placebo
Favors
carvedilol
Favors
placebo
All-cause mortality
Death or hospitalization
COPERNICUS: Carvedilol Prospective Randomized Cumulative Survival trial - SUMMARY -
In patients with severe chronic heart failure, carvedilol in addition to standard therapy reduced:
All-cause mortality
Combined endpoint of all-cause mortality and hospitalization for any reason
Effects were similar across all subgroups