CIBIS II: Cardiac Insufficiency Bisoprolol Study II
Purpose
To determine whether bisoprolol, a β1-selective adrenoreceptor blocker, reduces all-cause mortality in chronic heart failure
Reference
CIBIS-II Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999;353:9–13.
CIBIS II: Cardiac Insufficiency Bisoprolol Study II - TRIAL DESIGN -
Design
Multicenter, multinational, randomized, double-blind, placebo-controlled
Patients
2647 patients, aged 18–80 years, with left ventricular ejection fraction <35% and NYHA class III or IV heart failure, receiving standard therapy (diuretic plus ACE inhibitor/other vasodilator)
Follow up and primary end point
Mean 1.3 years follow up. Primary endpoint all-cause mortality
Treatment
Placebo or bisoprolol 1.25 mg daily, increased stepwise over several weeks as tolerated to target dose 10 mg daily
CIBIS II: Cardiac Insufficiency Bisoprolol Study II - RESULTS -
Study halted early because all-cause mortality significantly less in bisoprolol group than placebo group
Also significant reduction in:
Sudden deaths
All cardiovascular deaths
All-cause hospitalization, as well as hospitalization due to worsening heart failure
Treatment effects independent of severity or cause of heart failure
Drug well tolerated as defined by permanent early treatment withdrawals (15% in both groups, P=0.98)
CIBIS II: Cardiac Insufficiency Bisoprolol Study II - RESULTS continued-
All-cause mortality
CIBIS-II Investigators and Committees.
Lancet
1999;
353
:9
–
13.
P<0.0001
0
200
800
600
400
1.0
0.8
0.6
Days after inclusion
Survival
Placebo
Bisoprolol
CIBIS II: Cardiac Insufficiency Bisoprolol Study II - RESULTS continued-
P
Primary endpoint
All-cause mortality
Secondary endpoints
All-cause hospital admission
All cardiovascular deaths
Combined endpoint
Exploratory analyses
Sudden death
Hospital admission for
worsening heart failure
17
39
12
35
6
18
12
33
9
29
4
12
0.66 (0.54
–
0.81)
0.80 (0.71
–
0.91)
0.71 (0.56
–
0.90)
0.79 (0.69
–
0.90)
0.56 (0.39
–
0.80)
0.64 (0.53
–
0.79)
<0.0001
0.0006
0.0049
0.0004
0.0011
0.0001
Primary and secondary outcomes
CIBIS-II Investigators and Committees.
Lancet
1999;
353
:9
–
13.
Placebo
(n=1320)
(%)
Bisoprolol
(n=1327)
(%)
Hazard ratio
(95% CI)
CIBIS II: Cardiac Insufficiency Bisoprolol Study II - RESULTS continued-
0.4
0.6
0.8
1.0
Effect of bisoprolol on subgroups
1.2
1.4
1.6
1.8
Ischemia
Primary dilated
cardiomyopathy
Undefined
NYHA III
NYHA IV
Total
75/662
13/160
68/505
116/1106
40/221
121/654
15/157
92/509
173/1096
55/224
Relative risk (and 95% CI)
CIBIS-II Investigators and Committees.
Lancet
1999;
353
:9
–
13.
Baseline etiology/
functional class
Bisoprolol
(n/total)
Placebo
(n/total)
CIBIS II: Cardiac Insufficiency Bisoprolol Study II - SUMMARY -
In patients with class III or IV heart failure, bisoprolol in addition to standard therapy reduced:
All-cause mortality
Sudden death and cardiovascular death
All-cause hospitalization and hospitalization due to worsening heart failure