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