Beta-blockers after myocardial infarction: indication, ejection fraction, and de-escalation pathway

Dear Editor,

We read with great interest the landmark analysis by Rossello and colleagues, which examined beta-blocker therapy during the acute and chronic phases after myocardial infarction in patients without reduced left ventricular ejection fraction (LVEF). The authors found no reduction in death, reinfarction, or heart failure hospitalization in either period, whereas higher beta-blocker doses beyond 1 year were associated with worse outcomes.¹ These findings are clinically important, but their implementation requires careful attention to indication, phenotype, and deprescribing strategy.

First, beta-blocker deprescription should begin with reassessment of the indication rather than with the time elapsed since myocardial infarction. In routine cardiology practice, long-term beta-blocker therapy is often continued by inertia, but it may also be serving an active purpose beyond post-infarction secondary prevention. Relevant indications include angina, atrial fibrillation rate control, ventricular ectopy or non-sustained ventricular tachycardia, uncontrolled hypertension, residual ischaemia, aortic disease, or borderline ventricular dysfunction. The 2023 AHA/ACC chronic coronary disease guideline supports reassessing long-term beta-blocker use after myocardial infarction when LVEF is not reduced, and there is no angina, arrhythmia, uncontrolled hypertension, or other primary indication.² This distinction is essential because the REBOOT population excluded patients with clear alternative indications or contraindications to beta-blockers.¹ The trial should therefore not be interpreted as supporting discontinuation in all post-infarction patients. Rather, it challenges routine continuation when beta-blockers are used solely for secondary prevention in otherwise stable, revascularized patients without symptoms or ventricular dysfunction. In practice, the first step should be a medication-intent review: Why was the beta-blocker started, why is it still being continued, and what clinical risk would emerge if it were reduced or stopped? This review is particularly important at transitions of care, when discharge prescriptions can become chronic medications without explicit reassessment. Future post-infarction pathways should distinguish initiation, continuation, dose escalation, and withdrawal as separate decisions rather than treating beta-blocker therapy as a single therapeutic question.

Second, LVEF greater than 40% should not be treated as a single therapeutic category. In the REBOOT analysis, the signal in patients with LVEF 41–49% was not merely theoretical: during the first year, the primary endpoint occurred at 32.0 per 1000 patient-years in the beta-blocker group and 49.3 per 1000 patient-years in the no beta-blocker group, although the confidence interval was wide and statistical significance was not reached.¹ By contrast, patients with LVEF greater than 50% showed no comparable signal.¹ This distinction is clinically meaningful. Patients with LVEF 41–49% may have a residual-remodelling phenotype, larger infarct burden, subclinical heart failure vulnerability, or greater neurohormonal activation, even in the absence of overt heart failure. Such patients occupy a grey zone between uncomplicated myocardial infarction and early heart failure prevention, in which a neutral overall trial result may obscure a clinically relevant subgroup effect. Consistent with this interpretation, an individual patient data meta-analysis of randomized trials reported that beta-blockers reduced the composite of all-cause death, new myocardial infarction, or heart failure in patients with myocardial infarction and mildly reduced LVEF.³ By contrast, REDUCE-AMI showed no reduction in death or new myocardial infarction among patients with preserved LVEF.⁴ The hypothesis-generating interactions reported in REBOOT according to diabetes status during the first year and myocardial infarction type after the first year further suggest that treatment decisions should not rely on LVEF alone.¹ Future guidance should therefore separate patients with LVEF 41–49% from those with truly preserved LVEF, while also considering infarct type, diabetes, completeness of revascularization, resting heart rate, blood pressure, recurrent ischaemia, and early post-discharge LVEF recovery.

Third, if beta-blockers are to be de-escalated, the process should be structured and monitored. The apparent tension between REBOOT and ABYSS reflects different clinical questions. REBOOT primarily tested whether beta-blockers should be initiated at discharge after an uncomplicated myocardial infarction without reduced LVEF, whereas ABYSS tested interruption among patients who had already tolerated long-term beta-blocker therapy for a median of approximately 3 years after myocardial infarction.^1,5 These settings are not interchangeable: non-initiation at discharge does not necessarily imply that established long-term therapy can be stopped abruptly. A practical de-escalation pathway should include gradual, individualized dose reduction; early reassessment after each dose change; review of resting heart rate and blood pressure; evaluation of angina, palpitations, and exercise tolerance; and predefined criteria for treatment re-initiation. Such criteria might include recurrent angina, uncontrolled hypertension after withdrawal, clinically significant tachycardia or arrhythmia, documented ischaemia, or deterioration in LVEF. Patients with prior arrhythmias, incomplete revascularization, recurrent symptoms, high resting heart rate, or borderline LVEF may require ambulatory electrocardiographic monitoring or stress testing before and after de-escalation. The association between higher beta-blocker dose and worse chronic-phase outcomes in REBOOT should not be interpreted as proof of causality, but it reinforces the need to avoid automatic target-dose escalation in patients without heart failure or another clear indication.¹ Future studies should move beyond the binary question of beta-blocker use vs. non-use. Priorities include adequately powered trials in patients with LVEF 41%–49%, comparative evaluation of beta-blocker type and dose, and pragmatic trials testing structured tapering pathways with restart criteria, symptom burden, blood-pressure control, arrhythmia recurrence, and adherence to other secondary-prevention therapies as prespecified outcomes. This direction is consistent with contemporary guideline movement away from indefinite routine use and towards periodic reassessment of beta-blocker need after acute coronary syndrome.⁶

In conclusion, Rossello and colleagues provide important evidence against routine long-term beta-blocker therapy after uncomplicated myocardial infarction without reduced LVEF. The next clinical step should not be universal discontinuation, but indication-guided and phenotype-guided de-escalation. Reassessing active indications, distinguishing mildly reduced from preserved LVEF, and applying a structured tapering pathway may allow safer and more individualized beta-blocker management in contemporary post-infarction care.

Author contributions

N.Z. drafted the manuscript. Y.L. supervised the work, critically revised the manuscript, and approved the final version.

Funding

None declared.

Data availability

No new data were generated or analysed in support of this manuscript.