1. 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.

2. CIBIS II: Cardiac Insufficiency Bisoprolol Study II - TRIAL 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

3. 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)

4. CIBIS II: Cardiac Insufficiency Bisoprolol Study II - RESULTS continued-
All-cause mortality
Survival
1.0
0.8
0.6
Placebo
P<0.0001
Bisoprolol
200
400
600
800
Days after inclusion
CIBIS-II Investigators and Committees.
Lancet
1999;
353 :9 –
13.

5. CIBIS II: Cardiac Insufficiency Bisoprolol Study II - RESULTS continued-
Primary and secondary outcomes
Placebo
Bisoprolol
Hazard ratio
(n=1320)
(n=1327) P
(95% CI)
(%)
(%)
Primary endpoint
All-cause mortality 17 12
0.66 (0.54 –
0.81)
<0.0001
Secondary endpoints
All-cause hospital admission 39 33
0.80 (0.71 –
0.91)
0.0006
All cardiovascular deaths 12 9
0.71 (0.56 –
0.90)
0.0049
Combined endpoint 35 29
0.79 (0.69 –
0.90)
0.0004
Exploratory analyses
Sudden death 6 4
0.56 (0.39 –
0.80)
0.0011
Hospital admission for 18 12
0.64 (0.53 –
0.79)
0.0001
worsening heart failure
CIBIS-II Investigators and Committees.
Lancet
1999;
353 :9 –
13.

6. CIBIS II: Cardiac Insufficiency Bisoprolol Study II - RESULTS continued-
Effect of bisoprolol on subgroups
Baseline etiology/
Bisoprolol
Placebo
functional class
(n/total)
(n/total)
Ischemia
75/662
121/654
Primary dilated
13/160
15/157
cardiomyopathy
Undefined
68/505
92/509
NYHA III
116/1106
173/1096
NYHA IV
40/221
55/224
Total
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
Relative risk (and 95% CI)
CIBIS-II Investigators and Committees.
Lancet
1999;
353 :9 –
13.

7. 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