CIBIS II Cardiac Insufficiency Bisoprolol Study
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Transcript of CIBIS II Cardiac Insufficiency Bisoprolol Study
CIBIS IICardiac Insufficiency Bisoprolol Study
CIBIS IICardiac Insufficiency Bisoprolol Study
• Double-blind, placebo-controlled, randomised trial
• 2,647 patients included (NYHA III + IV)
• Bisoprolol administered on top of standard therapy(diuretic + ACE inhibitor)
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CIBIS II – Cardiac Insufficiency Bisoprolol Study Objectives
CIBIS II – Cardiac Insufficiency Bisoprolol Study Objectives
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• Primary objective– All-cause mortality
• Secondary objectives– Cardiovascular mortality
– Hospital admissions
– Cardiovascular mortality orcardiovascular hospital admissions
– Permanent treatment withdrawal
CIBIS II – Cardiac Insufficiency Bisoprolol Study Main inclusion criteria
CIBIS II – Cardiac Insufficiency Bisoprolol Study Main inclusion criteria
CIB
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aetiologies
• NYHA functional class III or IV
• Stable on ACE inhibitor and diuretic
• Aged 18 – 80 years
• Left ventricular ejection fraction 35%
CIBIS II – Cardiac Insufficiency Bisoprolol Study Design
CIBIS II – Cardiac Insufficiency Bisoprolol Study Design
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7.50
10.00
5.00
3.75
2.50
1.25
W1 W2 W3 W4 W5 W6 W7 W8 W9 W10W11W12W13W14W15W16 Week
Bisoprolol dose (mg)
No run-in period Dose increased according to tolerability
CIBIS II – Cardiac Insufficiency Bisoprolol Study Characteristics (I)
CIBIS II – Cardiac Insufficiency Bisoprolol Study Characteristics (I)
Placebo Bisoprolol(n=1320) (n=1327)
Demographic dataMean (range) age (years) 61 (22–80) 61 (26–80)Sex (M/F) 1062 (80%) 1070 (81%)
258 (20%) 257 (19%)
NYHA classIII 1096 (83%) 1106 (83%)IV 224 (17%) 221 (17%)
Heart failure Documented ischaemic heart disease 654 (50%) 662 (50%)Primary dilated cardiomyopathy 157 (12%) 160 (12%)Others* 509 (40%) 505 (38%)Mean (SD) left-ventricular ejection fraction 27.6 (5.5%)27.5 (6.0%)
*Coronary angiography unavailable or no history of myocardial infarction
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CIBIS II – Cardiac Insufficiency Bisoprolol StudyCharacteristics (II)
CIBIS II – Cardiac Insufficiency Bisoprolol StudyCharacteristics (II)
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Placebo Bisoprolol(n=1320) (n=1327)
Concomitant medication
Diuretic 1310 (99%) 1305 (98%)ACE inhibitor 1274 (96%) 1273 (96%)
Dihydropyridine-type calcium antagonist 23 (2%) 23 (2%)Nitrate 762 (58%) 773 (58%)Digoxin 670 (51%) 697 (53%)Amiodarone 206 (16%) 185 (14%)Anticoagulant 413 (31%) 399 (30%)Antiplatelet agent 558 (42%) 537 (40%)
CIBIS II – Cardiac Insufficiency Bisoprolol StudySurvival
CIBIS II – Cardiac Insufficiency Bisoprolol StudySurvival
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34% reduction in all-cause mortality with bisoprolol
1.0
0.8
0.6
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0 200 400 600 800Time after inclusion (days)
Su
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Bisoprolol: 156 deaths (n = 1327)
Placebo: 228 deaths (n = 1320)
log rank test, p < 0.0001
CIBIS II – Cardiac Insufficiency Bisoprolol StudyAnalysis of time to death
CIBIS II – Cardiac Insufficiency Bisoprolol StudyAnalysis of time to death
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Patients
Unknown causeof death
Non-cardio-vascular deaths
Other cardio-vascular deaths
Myocardialinfarction
Pumpfailure
Suddendeath
0.45(0.27 – 0.74)
0.75(0.37 – 1.50)
1.17(0.67 – 2.03)
0.85(0.31 – 2.34)
836%
p=0.0011
484%
363%
0.56(0.39 – 0.80)
0.74(0.48 – 1.14)
Hazard ratio:(95% CI)
p=0.17
p=0.75
p=0.58
p=0.41
p=0.0012
Bisoprolol (n = 1327)
Placebo (n = 1320)
0
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40
60
80
100
474%
71%
81%
282% 23
2%
141%
181%
232%
494%
CIBIS II – Cardiac Insufficiency Bisoprolol StudySecondary endpoints
CIBIS II – Cardiac Insufficiency Bisoprolol StudySecondary endpoints
CIB
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(log rank(n = 1320) (n = 1327) (95% Cl) test)
All-cause hospital admissions 513 (39%) 440 (33%) 0.80 (0.71–0.91) 0.0006
All cardiovascular deaths 161 (12%) 119 (9%) 0.71 (0.56–0.90) 0.0049
Combined endpoint 463 (35%) 388 (29%) 0.79 (0.69–0.90) 0.0004
Permanent treatment 192 (15%) 194 (15%) 1.00 (0.82–1.22) 0.98withdrawals
CIBIS II – Cardiac Insufficiency Bisoprolol StudyMortality by baseline findings
CIBIS II – Cardiac Insufficiency Bisoprolol StudyMortality by baseline findings
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Primary DCM 13/160
Undefined 68/505
NYHA III 116/1106
NYHA IV 40/221
121/654
Bisoprololn/total
Placebon/total
15/157
92/509
173/1096
55/224
Total
0.4Relative risk: 0.6 0.8 1.0 1.2 1.4 1.6 1.8
Mortality did not differ significantly between groupswhatever the aetiology or severity of heart failure
CIBIS II – Cardiac Insufficiency Bisoprolol StudyMain results at a glance
CIBIS II – Cardiac Insufficiency Bisoprolol StudyMain results at a glance
CIB
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reduction in
• All-cause mortality (independent of aetiology) by 34% (p<0.0001)
• Sudden death by 44% (p<0.0011)
• All-cause hospital admissions by 20% (p<0.0006)
• Hospital admissions due to worsening heart failure by36%
(p<0.0001)
CIBIS II – Cardiac Insufficiency Bisoprolol StudyConclusions
CIBIS II – Cardiac Insufficiency Bisoprolol StudyConclusions
• CIBIS II successfully demonstrated that ß1-selective bisoprolol – given in addition to standard therapy –reduces significantly all-cause mortality andall-cause hospitalisation in CHF patients.
• Bisoprolol is the first ß-blocker which has provenits efficacy in a single large-scale CHF studywith all-cause mortality as primary objective.
• Bisoprolol was as well tolerated as placebowith a permanent treatment withdrawal rate of 15% in both groups.