Problem Suspected acute MI
Format Double-blinded multi-center RCT
Treatment Metoprolol AND/OR Clopidogrel
Control Placebo
Population 45,852 patients
Inclusion criteria Patients who presented with ST elevation, left-bundle branch block, or ST depression within 24 h of the onset of the symptoms of suspected acute MI were potentially eligible for the study
-Provided that their responsible physician did not consider them to have clear indications for, or contraindications to, any of the study treatments.
Exclusion criteria PCI patients - because the combined use of aspirin plus clopidogrel (or ticlopidine) was likely to be considered indicated.

Otherwise, the exact reasons for excluding patients were determined by the responsible physician based on general guidance in the protocol, and included:
Small likelihood of worthwhile beneï¬Åt (e.g. other life-threatening disease or unconvincing history of MI)
High risk of adverse effects with the study treatments.

Criteria for a high risk of adverse effects with metoprolol would generally have included persistently low blood pressure (eg, systolic blood
pressure below 100 mm Hg), or low heart rate (eg, below 50 bpm), heart block, or cardiogenic shock.

Evidence of moderate heart failure (Killip II or III) was not an exclusion criteria.
Follow-up 28 days
Primary endpoint Co-primary endpoints of:
-Composite of death, reinfarction, or cardiac arrest (including ventricular ï¬Åbrillation)
-Death from any cause during the scheduled treatment period (ie, until ï¬Årst discharge or day 28).
Secondary endpoint(s) Reinfarction
Ventricular ï¬Åbrillation
Other cardiac arrest
Cardiogenic shock
Related conditions
Details .
Brief summary: Showed benefit of aspirin and clopidogrel in STEMI; increased adverse events in early metoprolol
PAPER: Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial.
Date 5 Nov 2005
Journal Lancet. 2005 Nov 5;366(9497):1622-32.
Information Beta-blocker (vs. placebo) immediately in AMI
-No difference in composite death, infarction or cardiac arrest
--Significantly adverse days 0-1
--Significantly beneficial day 1 onwards

-No difference in death
-Decreased reinfarction (OR 0.82; p=0.001) and VF (OR 0.83; p=0.001)
-Increase cardiogenic shock (OR 1.30; p<0.00001)
--Shock mainly days 0-1

-Proposes delaying beta-blockers until haemodynamically stable
PAPER: Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial.
Date 5 Nov 2005
Journal Lancet. 2005 Nov 5;366(9497):1607-21.
Information Clopdigrel (vs. placebo) in AMI (excluding PCI patients; including thrombolysis)
-Significant reduction in death, reinfarction, or stroke (RRR 9%; p=0.002)
--Corresponding to nine fewer events per 1000 patients treated for about 2 weeks
-Significant reduction in death (RRR 7%; p=0.03
-No difference in total of fatal/transfused/cerebral bleeds