CIBIS II: Cardiac Insufficiency Bisoprolol Study II

1
CIBIS II Cardiac Insufficiency Bisoprolol Study
II

• Purpose
• To determine whether bisoprolol, a ß1-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
  1999353913.

2
CIBIS II Cardiac Insufficiency Bisoprolol
Study II - TRIAL DESIGN -

• Design
• Multicenter, multinational, randomized,
  double-blind, placebo-controlled
• Patients
• 2647 patients, aged 1880 years, with left
  ventricular ejection fraction lt35 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, P0.98)

4
CIBIS II Cardiac Insufficiency Bisoprolol Study
II- RESULTS continued-

All-cause mortality
Survival
1.0
0.8
0.6
Placebo
Plt0.0001
Bisoprolol
0
200
800
600
400
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
P
(n1320)
(n1327)
(95 CI)
()
()
Primary endpoint
All-cause mortality
17
12
0.66 (0.54

0.81)
lt0.0001




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