Due caution using early β-blockers for acute myocardial infarction

Outcomes: The two pre-specified co-primary outcomes were: (1) composite of death, reinfarction, or cardiac arrest; and (2) death from any cause during the scheduled treatment period. Comparisons were by intention to treat, and used the log-rank method. This study is registered with ClinicalTrials.gov, number NCT 00222573. Results: Neither of the co-primary outcomes was significantly reduced by allocation to metoprolol. For death, reinfarction, or cardiac arrest, 2166 (9.4%) patients allocated metoprolol had at least one such event compared with 2261 (9.9%) allocated placebo (odds ratio [OR] 0.96, 95% CI 0.90–1.01; p=0.1). For death alone, there were 1774 (7.7%) deaths in the metoprolol group versus 1797 (7.8%) in the placebo group (OR 0.99, 0.92–1.05; p=0.69). Allocation to metoprolol was associated with fewer people having reinfarction (464 [2.0%] metoprolol vs. 568 [2.5%] placebo; OR 0.82, 0.72–0.92; p=0.001) and ventricular fibrillation (581 [2.5%] vs. 698 [3.0%]; OR 0.83, 0.75–0.93; p=0.001). Overall, these reductions were counterbalanced by more subjects developing cardiogenic shock (1141 [5.0%] vs. 885 [3.9%]; OR 1.30, 1.19–1.41; p<0.00001). This excess of cardiogenic shock was mainly during days 0–1 after admission, whereas the reductions in reinfarction and ventricular fibrillation emerged more gradually. Consequently, the overall effect on death, reinfarction, arrest, or shock was significantly adverse during days 0–1 and significantly beneficial thereafter. There was substantial net hazard in hemodynamically unstable patients, and moderate net benefit in those who were relatively stable (particularly after days 0–1).