1. 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/BMS
AstraZeneca
British Heart Foundation
UK Medical Research Council

2. COMMIT: Study design Mean treatment and follow-up: 16 days
TREATMENT: Metoprolol 15 mg iv over 15 mins, then 200 mg oral daily vs matching placebo
INCLUSION: Suspected acute MI (ST change or LBBB) within 24 h of symptom onset
EXCLUSION: Shock, systolic BP <100 mmHg, heart rate <50/min or II/III AV block
1 OUTCOMES: Death & death, re-MI or VF/arrest up to weeks in hospital (or prior discharge)
Mean treatment and follow-up: 16 days

3. COMMIT: Baseline characteristics
Characteristic Metoprolol Placebo (n=22,928) (n=22,923)
Aged % 26.0%
Time delay <6 h 34.0% 33.5%
SBP <120 mmHg 33.7% 33.5%
Anterior infarct 49.8% 49.6%
Killip class II 20.0% 19.8%
III 4.1% 4.2%
Fibrinolytic given 49.8% 49.7%

4. COMMIT: Treatment compliance
Compliance Metoprolol Placebo
(n=22,927) (n=22,923)
First iv dose given 98.5% 98.6%
3 iv doses completed 90.2% 96.0%
Oral treatment completed 86.2% 91.6%

5. COMMIT: Effects of METOPROLOL on
Reinfarction
Outcome
Metoprolol
Placebo
Odds ratio & 95% CI
after Re-MI
(22,927)
(22,922)
Metop. better
Placebo better
Died
206
(0.9%)
226
(1.0%)
Survived
261
(1.1%)
342
(1.5%)
18% SE 6
ALL COMBINED
467
(2.0%)
568
(2.5%)
(2P = 0.002)
0.4
0.7
1.0
1.3
1.6
1.9

6. Effects of iv then oral -blocker on reinfarction
in 3 major trials of acute MI
Trial
ß-blocker
Control
Odds ratio & 95% CI
(33,841)
(33,813)
ß-blocker better
Control better
MIAMI 85
(3.0%)
111
(3.8%)
ISIS-1
148
(1.8%)
161
(2.0%)
COMMIT
467
(2.0%)
568
(2.5%)
17% SE 5
OVERALL
700
(2.1%)
840
(2.5%)
(2P = )
0.4
0.6
0.8
1.0
1.2
1.4
1.6

7. COMMIT: Effects of METOPROLOL on Cardiac Arrest
Events
Metoprolol
Placebo
Odds ratio & 95% CI
(22,927)
(22,922)
Metop. better
Placebo better VF
582
(2.5%)
699
(3.0%)
17% SE 5
Other arrest
882
(3.8%)
899
(3.9%)
2% SE 5
5% SE 4
ANY OF ABOVE
1267
(5.5%)
1332
(5.8%)
(2P > 0.1; NS)
0.4
0.7
1.0
1.3
1.6
1.9

8. COMMIT: Effects of METOPROLOL on Death in hospital
Placebo:
1798 deaths (7.8%)
Metoprolol:
1776 deaths (7.7%)
1% (SE 3) relative risk reduction (2P=0.7)
% dead
Days since randomisation

9. COMMIT: Effects of METOPROLOL on Death by attributed cause(s)
Placebo
Odds ratio & 95% CI
(22,927)
(22,922)
Metop. better
Placebo better
Arrhythmia
388
(1.7%)
498
(2.2%)
22% SE 6
Shock
496
(2.2%)
384
(1.7%)
-29% SE 8
Other causes
892
(3.9%)
916
(4.0%)
3% SE 5
1% SE 3
ANY DEATH
1776
(7.7%)
1798
(7.8%)
(2P > 0.1; NS)
0.4
0.7
1.0
1.3
1.6
1.9

10. COMMIT: Effects of METOPROLOL on Cardiogenic Shock by day of event
Placebo
Odds ratio & 95% CI
(22,927)
(22,922)
Metop. better
Placebo better
475
(2.1%)
317
(1.4%) 1
282
(1.2%)
210
(0.9%) 2+
384
(1.7%)
361
(1.6%)
-29% SE 5
ALL
1141
(5.0%)
888
(3.9%)
(2P < )
0.4
0.7
1.0
1.3
1.6
1.9

11. COMMIT: Effects of METOPROLOL on Cardiogenic Shock by Killip class
Baseline
Metoprolol
Placebo
Odds ratio & 95% CI
Killip class
(22,927)
(22,922)
Metop. better
Placebo better I
611
(3.5%)
487
(2.8%) II
362
(7.9%)
296
(6.5%)
III
155
(16.2%)
100
(10.4%)
-29% SE 5
ALL
1141
(5.0%)
888
(3.9%)
(2P < )
0.4
0.7
1.0
1.3
1.6
1.9

12. COMMIT: Absolute effects of METOPROLOL on Re-MI, VF, Shock and Death by KILLIP class
at entry
Absolute differences per 1000
Re-MI VF
Shock
Death I 4 3 -7 II 10 11
-14
III -5
-58
-36
Any 5
-11 1

13. COMMIT: Effects of METOPROLOL on
Death, Re-MI or Arrest by prognosis & fibrinolytic
Baseline
Metoprolol
Placebo
Odds ratio & 95% CI
features
(22,927)
(22,922)
Metop. better
Placebo better
Prognostic index
Good
248
(3.3%)
284
(3.7%)
Average
575
(7.5%)
642
(8.4%)
Poor
1350
(17.6%)
1338
(17.5%)
Lytic given
Yes
1031
(9.0%)
1137
(10.0%) No
1142
(9.9%)
1127
(9.8%)
4% SE 3
ALL
2173
(9.5%)
2264
(9.9%)
(2P > 0.1; NS)
0.4
0.6
0.8
1.0
1.2
1.4
1.6

14. COMMIT: Effects of METOPROLOL on Death by shock index
Placebo
Odds ratio & 95% CI
index
(22,927)
(22,922)
Metop. better
Placebo better
Good
654
(4.1%)
719
(4.5%)
Average
569
(12.1%)
598
(12.6%)
Poor
553
(25.9%)
481
(23.4%)
1% SE 3
ALL
1776
(7.7%)
1798
(7.8%)
(2P > 0.1; NS)
0.4
0.7
1.0
1.3
1.6

15. COMMIT: Conclusions Slides available on: www.commit-ccs2.org
 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 (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< ), 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)
Slides available on: