Lancet 2005;366:1622-32Background Beta blockers were routinely used for the early management of patients with AMI; however, their efficacy and safety remained uncertain in this clinical scenario. Recall that in the BHAT trial, propranolol reduced death 2 years following an AMI with an NNT of approximately 33 but the cohort was highly selected, the drug was started, on average, 14 days following admission and those over the age of 70 were excluded. ISIS-1 found that atenolol reduced death with an NNT of approximately 100 when started immediately in lower risk AMI patients but treatment effect heterogeneity was observed in patient subgroups with higher risk features. The ClOpidogrel and Metoprolol Infarction Trial (COMMIT) sought to test the hypothesis that early beta-blockade with metoprolol would reduce cardiac events and death in a broad population of patients with AMI.Cardiology Trial’s Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients Patients with suspected myocardial infarction, who presented with ST elevation, left-bundle branch block, or ST depression within 24 hours of symptom onset were eligible. Patient eligibility was ultimately determined by the responsible physician but protocol guidance suggested the following relative contraindications: persistently low blood pressure (SBP <100 mmHg) or low heart rate (<50 bpm), heart block, or cardiogenic shock. Unlike previous trials, evidence of moderate heart failure (Killip II or III) was not an exclusion criteria. Baseline characteristics The average age of participants was 61 and the majority were male (72%). The mean SBP and heart rate at entry were 128 mmHg and 82 beats per minute, respectively. Less than 10% had a previous MI. ST elevation was present in 87% of patients, ST depression in 7%, and bundle branch block in 6%. Thirty percent of patients had heart rate ≥90 bpm upon admission and 7% of those had a heart rate ≥110 bpm. Thirty three percent of patients had SBP <120 mmHg at study entry. Approximately 25% of patients were classified as Killip class II (20%) corresponding to the presence of rales, crackles, an S3,  elevated JVP or pulmonary venous congestion on chest x-ray or Killip class III (5%) corresponding to frank pulmonary edema.Procedures This trial had a 2x2 factorial design but we will focus only on the metoprolol comparison. Following randomization, patients were immediately given metoprolol or placebo via the following sequence of interventions:* An immediate intravenous injection of 5 mg of metoprolol or matching placebo, given over 2- 3 minutes.* About 2-3 minutes later, if the heart rate was >50 bpm and the SBP was >90 mmHg, another 5 mg of metoprolol or matching placebo was injected.* About 2-3 minutes later, another 5 mg of metoprolol or matching placebo was injected if the heart rate and SBP met the above parameters.* 15 minutes after these intravenous doses, a 50 mg metoprolol or placebo tablet was to be given and repeated every 6 hours during days 0-1.* From day 2 onward, 200 mg of sustained-release metoprolol or placebo was to be given for up to 4 weeks or until hospital discharge (whichever came first) unless some definite contraindication was thought to have arisen.At hospital discharge or at day 28 (whichever came first), a single-sided follow-up form was to be completed. No further follow-up was sought. Post-discharge use of aspirin, beta-blocker, and other established therapies was encouraged but not monitored.Endpoints There were 2 prespecified co-primary outcomes. One was a composite of death, reinfarction or cardiac arrest and the other was all-cause death during the scheduled treatment period (i.e., until hospital discharge or day 28).The investigators estimated the event rate in the placebo group for the primary composite endpoint would be 14% prior to the start of the study; however, that estimate was reduced to 10% as the study proceeded. Thus