Beta-blockers post-MI: Should we stop using them if patients have normal heart function?

In contemporary medicine, the extent of evidence needed to stop recommending an existing therapy typically far exceeds the threshold required to introduce a new one. Novel therapies are often implemented in practice based on one or two large-scale randomized controlled trials (e.g., sodium-glucose cotransporter-2 inhibitors). However, multiple studies can demonstrate that a therapy is ineffective for a given condition, yet clinicians are often reluctant to abandon that medication once it has become part of the “usual” regimen. Such is the case with beta-blockers in patients who present with a myocardial infarction (MI) and have normal or near-normal heart function post-MI.Beta-blocker use post-MIHistorically, beta-blockers were recommended as part of the typical post-MI cocktail, in addition to a renin-angiotensin-aldosterone system inhibitor, a statin and dual antiplatelet therapy.1,2 This recommendation was primarily based on data before the routine use of reperfusion strategies, such as percutaneous coronary intervention (PCI) and fibrinolysis. Beta-blockers are strongly recommended in patients who have a left ventricular ejection fraction (LVEF) of ≤ 40%, as they have demonstrated a survival benefit in these patients.3 However, the effect of beta-blockers in patients who do not have left ventricular dysfunction after an MI (which is becoming increasingly common due to readily accessible reperfusion therapy) is less clear.Evidence for long-term use: In 2017, a Doctor of Pharmacy student and I conducted a systematic review to evaluate the evidence for long-term beta-blockers in patients post-MI without left ventricular dysfunction in the modern reperfusion era.4 Of the eight cohort studies we identified, only two demonstrated a reduction in all-cause death with beta-blockers, whereas no difference was observed in the other six studies. Among the eight studies, only four studies reported a major adverse cardiovascular event outcome (e.g., MI, stroke, heart failure hospitalization), none of which demonstrated a benefit with beta-blocker therapy. We concluded that this evidence imparted uncertainty regarding the benefit of beta-blockers in this population and suggested that they may be considered for discontinuation after one year.Following this systematic review, two noteworthy studies were published that both demonstrated futility with beta-blockers post-MI. An open-label trial conducted in Japan of 801 patients with an ST-segment elevation MI who underwent PCI ≤ 24 hours post-MI and had an LVEF ≥ 40%, were randomized to carvedilol or no beta-blocker therapy.5 After three years, the primary composite endpoint of adverse cardiovascular events (death, MI, or hospitalization for heart failure or acute coronary syndrome) was similar between groups (6.8% vs 7.9%, p=0.20), although the trial did not have a sufficient sample size to detect a significant difference.A well-designed Ontario-based cohort study evaluated exposure to beta-blocker versus no beta-blocker therapy in 33,811 patients ≥ 65 years of age who experienced an MI.6 Patients with a history of heart failure with reduced ejection (HFrEF) or who were prescribed carvedilol (which is limited to patients with HFrEF in Ontario) were excluded. The primary composite outcome of death or hospitalization for a recurrent MI or angina at one year was not significantly different between groups (14.8% vs 14.7%, adjusted hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.94–1.07).Recent randomized controlled trial data: Two open-label randomized controlled trials recently demonstrated conflicting results, which has fueled this debate. The REDUCE-AMI trial randomized 5,020 patients (mostly from Sweden) with an acute MI and LVEF ≥ 50% to either beta-blocker (metoprolol or bisoprolol) or no therapy.7 There was, however, some crossover between groups. After 3.5 years, no difference was seen in the primary outcome (all-cause death or recurrent MI) between patients assigned to a beta-blocker or not (7.9% vs 8.3%, HR 0.96, 95% CI 0.79–1.16), although the event rates were lower than anticipated. Cardiovascular death and all-cause death were similar between groups, as were safety endpoints (e.g., hospitalization for bradycardia).The ABYSS trial, conducted in France, included 3,698 patients with an MI and an LVEF ≥ 40% who underwent revascularization six months or more before randomization.8 Patients were randomized to either continue or discontinue their beta-blocker. The primary outcome of death, nonfatal MI, nonfatal stroke or hospitalization for a cardiovascular reason was lower in the group that continued their beta-blocker (21.1%) compared to those who interrupted therapy (23.8%) at three years, which did not meet the criteria for noninferiority. However, the main criticism of this trial is that the primary outcome was driven by hospitalizations for a coronary-related reason (e.g., suspected angina) and, due to the open-label design, clinicians who knew their patients were not on a beta-blocker may have been more likely to refer them to hospital.SummaryFor patients who present with an MI and have an LVEF ≥ 50% post-vascularization, the benefit of beta-blockers (if one truly exists) is likely modest at best. Therefore, it is reasonable to taper and discontinue beta-blockers in these patients, particularly older persons that are at higher risk of adverse effects, although the timeframe is unclear (e.g., 1-year post-MI). This does not apply to patients with an LVEF < 50% or those who did not undergo revascularization, or patients with another indication for beta-blocker therapy (e.g., atrial fibrillation). The recently published American College of Cardiology/American Heart Association guideline for the management of patients with acute coronary syndromes continues to recommend beta-blockers in all patients post-MI despite these new trial data, stating that more studies are needed.9 Fortunately, several ongoing (albeit open-label) trials, including one based in Edmonton,10 will provide more insight regarding this clinical question.Arden Barry is a clinical pharmacy and research specialist in ambulatory cardiology at the Jim Pattison Outpatient Care and Surgery Centre in Surrey, B.C., and associate professor (partner) at the Faculty of Pharmaceutical Sciences, University of British Columbia in Vancouver, B.C.References:O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013;127:e362-e425.Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;64:e139-e228.Ezekowitz JA, O’Meara E, McDonald MA, et al. 2017 Comprehensive update of the Canadian Cardiovascular Society guidelines for the management of heart failure. Can J Cardiol 2017;33:1342-433.Hong J, Barry AR. Long-term beta-blocker therapy after myocardial infarction in the reperfusion era: a systematic review. Pharmacotherapy 2018;38:546-54.Watanabe H, Ozasa N, Morimoto T, et al. Long-term use of carvedilol in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. PLoS One 2018;13:e0199347.Jackevicius CA, Krumholz HM, Ross JS, et al. Clinical outcomes with beta-blocker use in patients with recent history of myocardial infarction. Can J Cardiol 2020;36:1633-40.Yndigegn T, Lindahl B, Mars K, et al. Beta-blockers after myocardial infarction and preserved ejection fraction. N Engl J Med 2024;390:1372-81.Silvain J, Cayla G, Ferrari E, et al. Beta-blocker interruption or continuation after myocardial infarction. N Engl J Med 2024;391:1277-86.Rao SV, O’Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for the management of patients with acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2025;151:e771-e862.ClinicalTrials.gov. De-adoption of beta-blockers in patients with stable ischemic heart disease (ABBREVIATE). (accessed March 2, 2025).