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CLINICAL STATEMENTS AND GUIDELINES April 1, 2025 Circulation. 2025;151:e771–e862. DOI: 10.1161/CIR.0000000000001309 e800 4.6 Beta-Blocker Therapy Recommendation for Beta-Blocker Therapy Referenced studies that support recommendation are summarized in the Evidence Table. COR LOE Recommendation 1 A 1 In patients with ACS without contraindications, early (<24 hours) initiation of oral beta-blocker therapy is recommended to reduce risk of reinfarction and ventricular arrhythmias.1–5 Synopsis Beta blockers decrease myocardial oxygen demand by reducing the heart rate, blood pressure, and myocardial contractility.1,3 The clinical benefit of beta blockers in patients with left ventricular ejection fraction (LVEF) <40% and stabilized HF is well established, including patients post-MI.3–5 Most of the RCT data pertaining to early use of beta-blocker therapy in STEMI were conducted in the pre-reperfusion era.3 No adequately powered RCTs have been done that examine the clinical benefit of beta blockers during hospitalization among patients exclusively with NSTE-ACS. Although most studies were conducted in patients with STEMI, early hospital initiation of beta-blocker therapy (within 24 hours) is recommended among most patients with ACS and without contraindications (eg, acute HF [Killip class II-IV], evidence of low cardiac output state or at risk for cardiogenic shock, PR interval >0.24 milliseconds, second- or third-degree heart block without a cardiac pacemaker, severe bradycardia, active bronchospasm).1,2,6 Patients with an initial contraindication to beta-blocker therapy on presentation can be reassessed after 24 hours and initiated on oral beta-blocker therapy if the initial contraindication has resolved. Further study is warranted to examine the benefit in those patients with NSTE-ACS. Although an open-label randomized trial has raised questions about the benefit of long-term beta-blocker therapy following hospital discharge in patients with ACS who have undergone coronary revascularization and have preserved left ventricular (LV) function,7 this area remains under study. Recommendation-Specific Supportive Text 1 RCTs from both the pre-reperfusion era and in the early reperfusion era have shown that early initiation of beta-blocker therapy reduces the risk of reinfarction and ventricular arrhythmias among patients with STEMI.1–3 The COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction) trial included 45 852 patients (approximately 50% received fibrinolytic therapy and 7% having NSTE- ACS) and showed that early initiation of high doses (ie, up to 15 mg intravenously then 200 mg orally daily) of metoprolol reduced the risk of reinfarction and ventricular fibrillation compared with placebo but increased the risk of cardiogenic shock that occurred mainly during the first 24 hours.1 In a small open-label trial of 801 patients with STEMI who underwent PPCI, carvedilol did not reduce MACE over 3 years, but the trial was underpowered to detect a difference.8 Overall, the weight of the evidence suggests that a low dose of oral beta blocker should be initiated in patients without contraindication early after diagnosis of ACS (<24 hours) with slow dose escalation as blood pressure and heart rate permit. Use should be discontinued in those with new or worsening HF symptoms or signs of cardiogenic shock. In hemodynamically stable patients with STEMI who do not have acute HF, intravenous beta blockers can be administered prior to reperfusion if there are ongoing symptoms or a clinical indication for administration. The weight of the evidence does not support the routine use of intravenous beta blockers prior to PPCI because of inconsistent results as to whether it has any favorable effect on infarct size or clinical outcomes.9,10 The optimal duration of beta-blocker use remains unclear in patients with preserved LVEF. Although a randomized trial did not confirm long-term benefit from continued use of a beta blocker after hospital discharge in lower risk patients with preserved LV function who had undergone coronary revascularization,7 additional studies are ongoing in this space. 4.7 Renin-Angiotensin-Aldosterone System Inhibitors Recommendations for Renin-Angiotensin-Aldosterone System Inhibitors Referenced studies that support recommendations are summarized in the Evidence Table. COR LOE Recommendations 1 A 1. In high-risk patients with ACS (LVEF ≤40%, hypertension, diabetes mellitus, or STEMI with anterior location), an oral angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) is indicated to reduce all-cause death and MACE.1–6 1 B-R 2 In patients with ACS and LVEF ≤40%, and with HF symptoms and/or diabetes mellitus, a mineralocorticoid receptor antagonist is indicated to reduce all-cause death and MACE.7 2a A 3 In patients with ACS who are not considered high risk, an oral ACEi or an ARB is reasonable to reduce MACE.4 Synopsis Oral ACE inhibitors reduce all-cause death and MACE in patients with STEMI or NSTEMI, particularly when associated with high-risk features (LVEF ≤40%, hypertension, diabetes mellitus, or STEMI with anterior location).1–4,6 Even in AMI without high-risk features, use of an oral ACEi Downloaded from http://ahajournals.org by on October 7, 2026