commit/ccs-2 ( c l o pidogrel & m etoprolol in m yocardial i nfarction t rial)
DESCRIPTION
COMMIT/CCS-2 ( C l O pidogrel & M etoprolol in M yocardial I nfarction T rial). Designed, conducted, analysed and interpreted independently by COMMIT/CCS-2 collaboration Sources of funding (US$ 3M): SanofiAventis/BMS AstraZeneca British Heart Foundation UK Medical Research Council. - PowerPoint PPT PresentationTRANSCRIPT
COMMIT/CCS-2(ClOpidogrel & Metoprolol in Myocardial
Infarction Trial)
Designed, conducted, analysed and interpreted independently by COMMIT/CCS-2 collaboration
Sources of funding (US$ 3M): SanofiAventis/BMSAstraZenecaBritish Heart FoundationUK Medical Research Council
Beijing (48)
Shanghai (16)
Tianjin (21)
Shanxi (58)
Hebei (115)
Liaoning (92)
Jilin (50)
Heilongjiang (53)
Jiangsu (63)
Anhui (28)
Shandong (148)
Zhejiang (12)Jiangxi (20)
Fujian (22)Hunan (37)
Hubei (54)
Henan (121)
Guangdong (49)
Guizhou (11)
Hainan (7)
Sichuan (49)
Yunnan (12)
Shaanxi (43)
Gansu (25)
Qinghai (4)
Nei Mongol (38)
Guangxi (30)
Ningxia (8)
Xinjiang (7)
Chongqing (11)
COMMIT: 45,852 patients from 1250 centres in China
TREATMENT: Clopidogrel 75 mg daily vs placebo(aspirin 162mg daily in both groups)
INCLUSION: Suspected acute MI (ST change or LBBB) within 24 h of symptom onset
EXCLUSION: Primary PCI or high-risk of bleeding
1 OUTCOMES: Death & death, re-MI or stroke up to 4 weeks in hospital (or prior discharge)
Mean treatment and follow-up: 16 days
COMMIT: Study design
Characteristic Clopidogrel Placebo (n=22,960)
(n=22,891)
Age 70+ y 26.0% 26.0%
Female 27.7% 27.9%
Time delay <6 h 33.8% 33.7%
STEMI/LBBB 93.1% 93.1%
Killip class II/III 24.1% 24.0%
Fibrinolytic: All patients 49.7% 49.8%
STEMI <12h 67.8% 67.7%
COMMIT: Baseline characteristics
Therapy Clopidogrel Placebo (n=22,958) (n=22,891)
Anticoagulants 74.1% 75.0%
ACE inhibitors 68.2% 68.3%
Anti-arrhythmics 22.4% 22.2%
Nitrates 94.1% 94.3%
Diuretics 23.3% 23.3%
Calcium antagonists 11.8% 11.8%
COMMIT: Concomitant therapy
COMMIT: Effects of CLOPIDOGREL on Death, Re-MI or Stroke
Days since randomisation (up to 28 days)
Event (%)
9% (SE3) relative riskreduction (2P=0.002)
Placebo + ASA: 2311 events (10.1%)
Clopidogrel + ASA:2125 events (9.3%)
COMMIT: Effect of CLOPIDOGREL on Death in hospital
Dead(%)
Days since randomisation (up to 28 days)
Placebo + ASA: 1846 deaths (8.1%)
Clopidogrel +ASA:1728 deaths (7.5%)
7% (SE3) relative riskreduction (2P=0.03)
COMMIT: Effects of CLOPIDOGREL onReinfarction
Clopidogrel Placebo Odds ratio & 95% CIClopid. better Placebo better
Outcomeafter Re-MI (22,958) (22,891)
Died 209 223(0.9%) (1.0%)
Survived 273 330(1.2%) (1.4%)
ALL COMBINED 482 553(2.1%) (2.4%)13% SE 6(2P = 0.02)
0.4 0.6 0.8 1.0 1.2 1.4 1.6
COMMIT: Effects of CLOPIDOGREL onany Stroke
Clopidogrel Placebo Odds ratio & 95% CIClopid. better Placebo better
Types(22,958) (22,891)
Ischaemic 162 192(0.7%) (0.8%)
Haemorrhagic 55 55(0.2%) (0.2%)
ALL COMBINED 216 249(0.9%) (1.1%)14% SE 9
(2P > 0.1; NS)
0.4 0.6 0.8 1.0 1.2 1.4 1.6
Type Clopidogrel Placebo (n=22,958) (n=22,891)
CerebralFatal 39 40
Non-fatal 16 15
Non-cerebralFatal 36 37Non-fatal 46 36
Any major bleed 134 124 (0.58%) (0.54%)
COMMIT: Major bleed in hospital
COMMIT: Effects of CLOPIDOGREL onDeath, Re-MI or Stroke by day of event
Clopidogrel Placebo Odds ratio & 95% CIClopid. better Placebo better
Day of event(22,958) (22,891)
0 463 523(2.0%) (2.3%)
1 486 527(2.1%) (2.3%)
2-3 449 451(2.0%) (2.0%)
4-7 432 463(1.9%) (2.0%)
8-28 295 347(1.3%) (1.5%)
ALL 2125 2311(9.3%) (10.1%)9% SE 3
(2P = 0.002)
0.4 0.6 0.8 1.0 1.2 1.4 1.6
COMMIT: Effects of CLOPIDOGREL onDeath, Re-MI or Stroke by sex and age
Clopidogrel Placebo Odds ratio & 95% CIClopid. better Placebo better
Baselinefeatures (22,958) (22,891)
SexMale 1276 1416(7.7%) (8.6%)
Female 849 895(13.3%) (14.0%)
Age (years)<60 487 513(5.1%) (5.4%)
60-69 747 835(10.2%) (11.2%)
70+ 891 963(14.9%) (16.2%)
ALL 2125 2311(9.3%) (10.1%)9% SE 3
(2P = 0.002)
0.4 0.6 0.8 1.0 1.2 1.4 1.6
COMMIT: Effects of CLOPIDOGREL onDeath, Re-MI or Stroke by delay & fibrinolytic
Clopidogrel Placebo Odds ratio & 95% CIClopid. better Placebo better
Baselinefeatures (22,958) (22,891)
Hour to entry0-6 776 904(9.3%) (10.9%)
7-12 672 735(9.7%) (10.7%)
13-24 666 666(8.8%) (8.7%)
Lytic givenYes 1005 1123(8.8%) (9.9%)
No 1120 1188(9.7%) (10.3%)
ALL 2125 2311(9.3%) (10.1%)9% SE 3
(2P = 0.002)
0.4 0.6 0.8 1.0 1.2 1.4 1.6
From ISIS-2 to COMMIT: Effects of aspirin and clopidogrel on Death, Re-MI or Stroke
ISIS-2: Placebo 14%
ASA 10%
COMMIT: ASA 10%
ASA + Clop. 9%
ASA + Clopidogrel vs nil: ~50 per 1000 treated
~40 per 1000
~10 per 1000
COMMIT: Conclusions
Adding 75 mg daily CLOPIDOGREL to aspirin in acute MI prevents ~10 major vascular events per 1000 treated
No excess of cerebral, fatal or transfused bleeds (even with fibrinolytic therapy and in older people)
Each million MI patients treated for ~2 weeks would avoid 5000 deaths and 5000 non-fatal events
Slides available on: www.commit-ccs2.org