Highlight
- Beta blocker therapy withholding or withdrawal post-myocardial infarction (MI) in patients with preserved left ventricular ejection fraction (LVEF >40%) does not increase the short-term risk of ischaemic events.
- No significant difference in recurrent ischaemic events over a median 3.7-year follow-up was observed between patients randomized to beta blocker therapy or no beta blocker.
- Prior chronic beta blocker use before MI does not modify the safety profile of beta blocker withdrawal after MI in this population.
Study Background and Disease Burden
Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Beta blockers have long been recommended after MI to reduce reinfarction risk and prevent ventricular arrhythmias, based largely on evidence from earlier eras of cardiac care. Current international guidelines generally advocate initiation and continuation of beta blockers following MI irrespective of the patient’s left ventricular ejection fraction (LVEF). However, modern advances in reperfusion strategies and secondary prevention, as well as evolving evidence, have brought into question the universal benefit of beta blockers for patients without reduced LVEF (i.e., LVEF >40%).
Emerging clinical trials suggest that continued beta blocker therapy may not confer substantial ischaemic risk reduction in patients with preserved systolic function. Despite this, uncertainty remains about the safety of withholding or withdrawing beta blockers at hospital discharge in this subgroup, particularly regarding the risk of short-term and recurrent ischaemic events, which include cardiac death, reinfarction, ventricular arrhythmias, cardiac arrest, or need for unplanned revascularization.
Addressing this knowledge gap is highly clinically relevant to optimize cardiovascular pharmacotherapy post-MI, avoid unnecessary medication exposure, and minimize adverse effects associated with beta blockers, such as fatigue, bradycardia, and hypotension.
Study Design
This article presents a post hoc analysis of the randomized REBOOT trial, which enrolled patients with MI and preserved LVEF (>40%) to evaluate the effect of beta blocker therapy versus no beta blocker at hospital discharge.
– Population: 8,438 patients from the intention-to-treat cohort, with LVEF >40%, and documented beta blocker history in 8,401 subjects.
– Intervention: Randomization to beta blocker therapy initiation/continuation or withholding at hospital discharge.
– Comparator: No beta blocker therapy (either withheld initially or withdrawn after prior chronic use).
– Endpoints: The primary assessments were short-term (3-month) and long-term (median 3.7 years) incidence of a composite ischaemic endpoint encompassing cardiac death, reinfarction, sustained ventricular tachycardia or fibrillation, resuscitated cardiac arrest, or unplanned revascularization.
– Stratification: Analyses included subgroup evaluation based on chronic beta blocker use prior to index MI.
Key Findings
– Among 8,401 patients with beta blocker history documented, only 12.1% were on chronic beta blocker therapy before MI.
– At 3 months, beta blocker withholding or withdrawal was not associated with a statistically significant increase in short-term ischaemic events (HR 1.13, 95% CI 0.74–1.72), indicating safety in early post-discharge period.
– Over the median 3.7 years follow-up, recurrent ischaemic event rates did not differ significantly between randomized groups (HR 0.98, 95% CI 0.82–1.16).
– No significant interaction was found between prior beta blocker use and outcomes, suggesting that chronic beta blocker users did not have increased risk if beta blockers were withdrawn post-MI (HR for composite endpoint 0.93, 95% CI 0.64–1.34).
These findings demonstrate that in patients with MI but preserved LVEF, beta blocker therapy may be safely withheld or withdrawn at hospital discharge without increasing the risk of either short-term or long-term ischaemic events including cardiac death, reinfarction, or life-threatening arrhythmias.
Expert Commentary
The results of this post hoc REBOOT trial analysis challenge the dogma of universal beta blocker use after MI irrespective of left ventricular function. This data aligns with recently published studies suggesting limited benefit of beta blockers in patients without systolic dysfunction, possibly reflecting improvements in reperfusion therapy, statin use, and more comprehensive secondary prevention measures.
The absence of increased ischaemic risk upon beta blocker withdrawal in those previously treated chronically may relieve clinicians about potential safety concerns, enabling more personalized cardiac medication strategies. However, this study’s post hoc nature and the inherent limitations of composite endpoint interpretation warrant cautious extrapolation.
Limitations include potential residual confounding, lack of detailed mechanistic data, and the predominantly stable post-discharge patient population included. Future prospective trial data, along with mechanistic studies examining beta blocker pharmacodynamics and cardiac remodeling in preserved LVEF cohorts, would strengthen evidence.
Current guidelines may need to reconsider recommending beta blockers unconditionally following MI and instead adopt a more discriminating approach considering LVEF and individual patient risk profiles.
Conclusion
This post hoc analysis from the REBOOT trial provides compelling evidence supporting the safety of beta blocker withholding or withdrawal in patients with myocardial infarction and preserved left ventricular function (LVEF >40%). No significant increase in short-term or recurrent ischaemic events was observed.
These findings inform clinical decision-making by questioning the indiscriminate continuation of beta blockers following MI in this population, emphasizing the potential for tailored therapy to optimize patient outcomes, minimize adverse effects, and reduce polypharmacy.
Future research should focus on prospective randomized trials and real-world registries to validate these findings and guide guideline updates that pragmatically balance risks and benefits of beta blocker therapy after MI in patients without reduced ejection fraction.
References
Rossello X, Sánchez PL, Owen R, Raposeiras-Roubín S, Poletti F, Barrabés JA, et al. Effect of beta blocker withholding or withdrawal after myocardial infarction without reduced ejection fraction on ischaemic events: a post hoc analysis from the REBOOT trial. EuroIntervention. 2025 Aug 30:EIJ-D-25-00826. doi: 10.4244/EIJ-D-25-00826. Epub ahead of print. PMID: 40887991.
Ibanez B, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. European Heart Journal. 2020.
Bangalore S, et al. Beta-blocker use and clinical outcomes in stable outpatients with and without coronary artery disease. J Am Coll Cardiol. 2012.
Roffi M, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2016.
