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May 3, 2022 Circulation. 2022;145:e895–e1032. DOI: 10.1161/CIR.0000000000001063 e922

CLINICAL STATEMENTS AND GUIDELINES

practice guidelines. The benefits of mineralocorticoid receptor antagonists (MRA) after MI have mostly been shown in patients with symptomatic HFrEF.32–34 ARNi have not been well studied in stage B HF. The PARADISE-MI (Prospective ARNi vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction) study35 will report the efficacy and safety of sacubitril/valsartan in patients after acute MI, with LVEF ≤40 and/or pulmonary congestion, plus an additional risk-enhancing factor, compared with ramipril.

Recommendation-Specific Supportive Text

1.	 ACEi have been shown to impede maladaptive remodeling after acute MI in patients with reduced LVEF.36,37 In survivors of acute MI with asymptomatic LV dysfunction (LVEF <35%–40%), RCTs have shown that ACEi reduced mortality, HF hospitalizations, and progression to severe HF compared with placebo.2,4 Similarly, in those individuals with asymptomatic LV dysfunction in the SOLVD (Studies of Left Ventricular Systolic Dysfunction) prevention trial, which included approximately 20% without ischemic heart disease, enalapril was associated with reduced HF hospitalization and mortality compared with placebo.1,3 2.	 In multiple RCTs,42 statins have been shown to prevent adverse CAD events in patients with an MI, ACS, and with high cardiovascular risk. These trials have also shown that statin therapy reduces the risk of incident HF.5–9 A meta-analysis of 6 RCTs of >110 000 patients with an ACS showed that intensive statin therapy reduced hospitalizations for HF.5 A subsequent, larger collaborative metaanalysis of up to 17 major primary and secondary prevention RCTs showed that statins reduced HF hospitalization.42 These data support the use of statins to prevent symptomatic HF and cardiovascular events in patients with acute MI or ACS. 3.	 Two major trials have compared ARB with ACEi after MI. The VALIANT (Valsartan in Acute Myocardial Infarction) trial, which included approximately 25% of patients with asymptomatic LV dysfunction, showed that the benefits of valsartan on mortality and other adverse cardiovascular outcomes were comparable to captopril.10,38 In the OPTIMAAL (Optimal Trial in Myocardial Infarction with the Angiotensin II Antagonist Losartan) trial, losartan did not meet the noninferiority criteria for mortality compared with captopril.39 It has been hypothesized that the lower dose of losartan (50 mg daily) in the OPTIMAAL trial may have contributed to the greater difference than those seen with valsartan in VALIANT.40 No clinical trials have specifically evaluated ARB in patients with asymptomatic reduced LVEF in the absence of previous MI. Although ARB are alternatives for patients with ACEi-induced angioedema, caution is advised because some patients have also developed angioedema with ARB. 4.	 Current evidence supports the use of beta blockers to improve adverse cardiac remodeling and outcomes in patients with asymptomatic reduced LVEF after MI. Among patients with a recent MI and reduced LVEF, carvedilol reduced maladaptive remodeling41 and reduced mortality compared with placebo.11 Among patients with asymptomatic LV systolic dysfunction in the SOLVD prevention trial (which included 80% with previous MI) and the SAVE (Survival and Ventricular Enlargement) trial, secondary analyses showed that the administration of beta blockers in addition to ACEi reduced mortality and hospitalization.12,13

Table 10.  Other ACC/AHA Clinical Practice Guidelines Addressing Patients With Stage B HF Consideration Reference Patients with an acute MI who have not developed HF symptoms treated in accordance with GDMT 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction51

2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes52

Coronary revascularization for patients without symptoms of HF in accordance with GDMT 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction53 (This guideline has been replaced by Lawton, 2021.54)

2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease55 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery56 (This guideline has been replaced by Lawton, 2021.54)

Valve replacement or repair for patients with hemodynamically significant valvular stenosis or regurgitation and no symptoms of HF in accordance with GDMT 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease.57,58 Patients with congenital heart disease that may increase the risk for the development of HF 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease59 AATS indicates American Association for Thoracic Surgery; ACC, American College of Cardiology; ACCF, American College of Cardiology Foundation; AHA, American Heart Association; GDMT, guideline-directed medical therapy; HF, heart failure; MI, myocardial infarction; PCNA, Preventive Cardiovascular Nurses Association; SCAI, Society for Cardiovascular Angiography and Interventions; and STS, The Society of Thoracic Surgeons. Downloaded from http://ahajournals.org by on October 7, 2026