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Beta-adrenergic receptor antagonists, or β-blockers, have been a cornerstone of treatment in patients with acute coronary syndromes (ACS) for more than 4 decades. First studied in the 1960s, β-blockers in ACS have been shown to decrease the risk of death, recurrent ischemic events, and arrhythmias by reducing catecholamine-mediated effects and reducing myocardial oxygen demand. Through the decades, the β-blocker of choice, timing of initiation, duration of therapy, and dosing have evolved considerably. Despite having clear benefits in certain patient populations (eg, patients with systolic dysfunction who are hemodynamically stable), the benefit of β-blockers in other populations (ie, in patients at low risk for complications receiving modern revascularization therapies and optimal medical management) remains unclear. This article provides a review of the landmark clinical trials of β-blockers in ACS and highlights the chronology and evolution of guideline recommendations through the decades.