COMMIT/CCS-2(ClOpidogrel & Metoprolol in Myocardial

Infarction Trial)

By

Dr Salman Ahmed

FCPS-II cardiology trainee

Effect of Beta blocker on mortality was studied in low risk pts showed reduced mortality and were carried on small population

Effect of IV Beta blockers was still unclear

Effect of clopidogrel was studied before this trial on NSTEMI and pts undergoing PCI shows benefit but still it was not studied in STEMI

This was placebo control trail to see seperatelyefficacy of clopidogrel and iv metoprolol than oral in pts with MI

TREATMENT: Metoprolol 15 mg iv over 15 mins, then 200 mg oral daily vs matching placebo

INCLUSION: Suspected acute MI (ST change orLBBB) within 24 h of symptom onset

EXCLUSION: Shock, systolic BP <100 mmHg, heart rate <50/min or II/III AV block

OUTCOMES: Death , re-MI ,VF/arrest & shock up to 4 weeks in hospital (or prior discharge)

Mean treatment and follow-up: 16 days

COMMIT: Study design

Pt were given metoprolol iv 5mg then it was repeated untill pts heart rate was >50 b/min or SBP>90 mmHg

Mean time to presentation of Pts was about 10 h

After 15 min: of IV pt was given 50 mg was continued day 0-1 and next day 200mg was started

Characteristic Metoprolol Placebo (n=22,928) (n=22,923)

Aged 70+ 26.1% 26.0%

Mean Age 61.1 61

Time delay <6 h 34.0% 33.5%

Previous HTN 43.1% 43.0%

SBP <120 mmHg 33.7% 33.5%

Anterior infarct 49.8% 49.6%

Killip class I 75.3% 75.6%

II 20.0% 19.8%

III 4.1% 4.2%

Fibrinolytic given 49.8% 49.7%

COMMIT: Baseline characteristics

Compliance Metoprolol Placebo

(n=22,927) (n=22,923)

First iv dose given 98.5% 98.6%

3 iv doses completed 90.2% 96.1%

Oral treatment completed 86.2% 91.6%

COMMIT: Effects of METOPROLOL on

Reinfarction

Metoprolol Placebo Odds ratio & 95% CI

Metop. better Placebo better

Outcome

after Re-MI (22,927) (22,922)

Died 206 226(0.9%) (1.0%)

Survived 261 342(1.1%) (1.5%)

ALL COMBINED 467 568(2.0%) (2.5%)18% SE 6

(2P = 0.002)

0.4 0.7 1.0 1.3 1.6 1.9

COMMIT: Effects of METOPROLOL on Death

by attributed cause(s)

Metoprolol Placebo Odds ratio & 95% CI

Metop. better Placebo better

Cause(s)

(22,927) (22,922)

Arrhythmia 388 498(1.7%) (2.2%) 22% SE 6

Shock 496 384(2.2%) (1.7%) -29% SE 8

Other causes 892 916(3.9%) (4.0%) 3% SE 5

ANY DEATH 1776 1798(7.7%) (7.8%)1% SE 3

(2P > 0.1; NS)

0.4 0.7 1.0 1.3 1.6 1.9

More pts in metoprolol group suffered cariogenic shock than placebo

Majority of Cardiogenic shock occurred during day 0-1

Pts having low probability of shock less no of pts sufferd from shock

Incidence of VF,ReMI was almost equal during 0-1

Outcome was worse from 0-1 and then improved gradually thereafter

COMMIT: Effects of METOPROLOL on

Cardiogenic Shock by day of event

Metoprolol Placebo Odds ratio & 95% CI

Metop. better Placebo better

Day of event

(22,927) (22,922)

0 475 317(2.1%) (1.4%)

1 282 210(1.2%) (0.9%)

2+ 384 361(1.7%) (1.6%)

ALL 1141 888(5.0%) (3.9%)-29% SE 5

(2P < 0.00001)

0.4 0.7 1.0 1.3 1.6 1.9

COMMIT: Effects of METOPROLOL on

Cardiogenic Shock by Killip class

Metoprolol Placebo Odds ratio & 95% CI

Metop. better Placebo better

Baseline

Killip class (22,927) (22,922)

I 611 487(3.5%) (2.8%)

II 362 296(7.9%) (6.5%)

III 155 100(16.2%) (10.4%)

ALL 1141 888(5.0%) (3.9%)-29% SE 5

(2P < 0.00001)

0.4 0.7 1.0 1.3 1.6 1.9

COMMIT: Effects of METOPROLOL on

Death by shock index

Metoprolol Placebo Odds ratio & 95% CI

Metop. better Placebo better

Shock

index (22,927) (22,922)

low 654 719(4.1%) (4.5%)

Medium 569 598(12.2%) (12.6%)

High 553 481(25.9%) (23.4%)

ALL 1776 1798(7.7%) (7.8%)1% SE 3

(2P > 0.1; NS)

0.4 0.7 1.0 1.3 1.6

Metoprolol (15 mg iv, then 200 mg oral daily) in acute MI did not significantly reduce mortality in hospital

It reduced the absolute risks of reinfarction by 5 per 1000 (P=0.001) and of VF by 5 per 1000 (P<0.001)

But, overall, it increased the risk of cardiogenic shock by 11 per 1000 (P<0.00001), chiefly on days 0-1

In acute MI, it may be better to start beta-blocker when the patient is stable (and then continue long-term)

Pts were given aspirin 162 mg along with clopidogrel 75 mg without giving loading dose within 24 hours of symptoms

Pts who undergoes PCI were excluded from the study

Treatment continued upto discharge or 28 days

Primary outcome was (1) the composite of death, reinfarction, or stroke; and (2) death from any cause during the scheduled treatment period.

Characteristic Clopidogrel Placebo (n=22,928) (n=22,923)

Aged 70+ 26.0% 26.0%

Mean Age 61.3 61.4

Time delay <6 h 33.7% 33.7%

ST elevation 86.5% 86.9%

LBBB 6.6% 6.2%

Anterior infarct 49.8% 49.6%

Previous HTN 43.1% 43.0%

Fibrinolytic given 49.8% 49.7%

COMMIT: Baseline characteristics

Outcome Clopidogrel Placebo

(n=22,961) (n=22,891)

Reinfarction 1.2% 1.4%

Stroke 0.6% 0.6%

Death (any cause) 7.5% 8.1%

Composite 9.2% 10.1%

Figure 3

Source: The Lancet 2005; 366:1607-1621 (DOI:10.1016/S0140-6736(05)67660-X)

Terms and Conditions

Figure 2

Source: The Lancet 2005; 366:1607-1621 (DOI:10.1016/S0140-6736(05)67660-X)

Terms and Conditions

There was greater benefit when it was started <6h and pts receiving >12 have equal mortality

There no inc: in major bleeding during study however minor bleed was increased

There was 10 fewer event per thousand in term of death,reinfarction and CVA

Source: The Lancet 2005; 366:1607-1621 (DOI:10.1016/S0140-6736(05)67660-X)

Terms and Conditions

Clopidogrel placebo Excess/1000

Fatal 73(0.32%)

74(0.32%)

-0.1

cerebral 39(0.17%)

41(0.18%)

Non cerebral 36(0.16%)

37(0.16%)

nonfatal 61(0.27%)

52(0.22%)

0.4

overall 134(0.58%)

125(0.55%)

0.4

patients with acute MI, adding clopidogrel 75 mg daily to aspirin and other standard treatments (such as fibrinolytic therapy) safely reduces mortality and major vascular events in hospital, and should be considered routinely

It reduced aditional reduction of 10 death,reMIand stroke per 1000 patients treated