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CLINICAL STATEMENTS AND GUIDELINES Circulation. 2025;151:e771–e862. DOI: 10.1161/CIR.0000000000001309 April 1, 2025 e801 confers a modest survival benefit.4 Compared with ACEi, the benefits of an ARB in patients with AMI with HF or LV systolic dysfunction are similar.5 Thus, in the absence of contraindications, either an oral ACEi or ARB should be initiated in appropriate patients with AMI.5,8 In patients with AMI with LVEF ≤40%, and with HF symptoms and/ or diabetes mellitus, the addition of a mineralocorticoid receptor antagonist reduced all-cause death and MACE and should be given in the absence of advanced chronic kidney disease, hyperkalemia, or other contraindication. In patients with symptomatic HF and reduced LVEF, sacubitril-valsartan has been demonstrated to be superior to an ACEi for reducing cardiovascular death or HF hospitalization; however, the trial excluded patients within 3 months of ACS.9 In a trial of patients early after MI with LVEF ≤40% and/or pulmonary congestion, sacubitril-valsartan did not significantly reduce cardiovascular death or incident HF compared with an ACEi. Hypotensive events were more common with sacubitril-valsartan, but no other safety concerns were observed. Therefore, if treatment with sacubitril-valsartan for HF with reduced ejection fraction is planned, initiation of this combination agent instead of an ACEi or ARB early after MI appears safe.10 Recommendation-Specific Supportive Text 1 Randomized controlled trials have demonstrated a reduction in all-cause death and MACE with the addition of an oral ACEi in patients with AMI with LVEF ≤40%1,3 and in patients with anterior STEMI.2 An individual-patient meta-analysis of 98 496 patients with AMI also showed a survival benefit with ACEi use, with the greatest absolute benefit in patients with hypertension, diabetes, and STEMI of anterior location.4 In the VALIANT (Valsartan in Acute Myocardial Infarction) trial of patients with AMI with LV systolic dysfunction and/ or HF symptoms, the use of an ARB was statistically noninferior to an ACEi, and rates of all-cause death were similar between the 2 treatment arms.5 Concomitant initiation of both an ACEi and ARB in patients with AMI should be avoided due to an increase in adverse events without added benefit compared with either drug alone.5,8 2. In the EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) trial, the mineralocorticoid receptor antagonist eplerenone reduced both all-cause death and MACE during a mean follow-up of 16 months in patients with AMI with LVEF ≤40% who also had symptoms of HF and/or diabetes mellitus. The use of evidence-based therapies for this population was relatively high, including 86% use of ACEi or ARB and 75% use of a beta blocker at enrollment.7 Patients with advanced chronic kidney disease (serum creatinine >2.5 mg/dL) or hyperkalemia (serum potassium >5.0 mmol/L) were excluded from enrollment.7 In a trial of 1012 patients with acute STEMI and without a history of HF, the use of eplerenone reduced the primary endpoint compared with placebo, but the benefit was largely driven by a reduction in natriuretic peptides.11 3. The ACE Inhibitor Myocardial Infarction Collaborative Group meta-analysis of 98 496 patients with AMI reported a 30-day mortality rate of 7.1% in AMI patients treated with an ACEi compared with 7.6% receiving placebo (proportional reduction, 7% [95% CI, 2-11]; P =0.004), and the benefit appeared to be irrespective of baseline risk.4 The use of an ACEi also reduced nonfatal cardiac failure compared with placebo.4 5 STEMI MANAGEMENT: REPERFUSION STRATEGIES 5.1 Regional Systems of STEMI Care Recommendation for Regional Systems of STEMI Care Referenced studies that support recommendation are summarized in the Evidence Table. COR LOE Recommendation 1 B-NR 1 All communities should create and maintain regional systems of STEMI care that coordinate prehospital and hospital-based STEMI care processes with the goal of reducing total ischemic time and improving survival in patients with STEMI.1–6 Synopsis The goal of optimizing outcomes after STEMI depends not only on the efficient execution of STEMI care processes but also on the seamless communication and coordination of care among the teams caring for the patient. The goal of each community is therefore to ensure a coordinated response to every patient with STEMI, regardless of physical location at presentation, to help minimize total ischemic time. The creation and maintenance of successful systems of STEMI care require detailed mapping of care for all possible routes by which a patient with STEMI could present for diagnosis and receive definitive reperfusion therapy at both PCI-capable and non–PCIcapable facilities, as well as access to cardiac surgical care and other advanced care modalities (Figure 6). The many stakeholders of regional systems of STEMI care (including hospitals, EMS companies, regional public health departments, and local governments) must ensure that all components of a STEMI system of care function in a coordinated way with no gaps in care processes to help optimize STEMI outcomes in the community. Recommendation-Specific Supportive Text 1 The establishment of coordinated regional systems of STEMI care is associated with reduced time to Downloaded from http://ahajournals.org by on October 7, 2026