6 Minutes
New evidence challenges a 40-year standard in heart attack care
For more than four decades, beta blockers have been part of routine therapy for patients recovering from myocardial infarction (heart attack). However, the international REBOOT trial — the largest randomized study to date on this question — found that continuing beta-blocker therapy after hospital discharge provides no clear clinical benefit for patients who retain normal cardiac function. Even more concerning, a prespecified subgroup analysis detected an increased risk of adverse outcomes among women prescribed these drugs following an uncomplicated heart attack.
Study design, scale and primary findings
The REBOOT trial enrolled 8,505 patients across 109 hospitals in Spain and Italy. Participants who had experienced an uncomplicated myocardial infarction and were discharged with preserved left ventricular ejection fraction (LVEF) were randomized to either continue beta-blocker therapy or omit it. All other guideline-directed treatments were provided consistently across groups, and patients were followed for a median of roughly 3.7 to 4 years.
Primary endpoints included all-cause mortality, recurrent myocardial infarction, and hospitalization for heart failure. Across the entire study population, there were no statistically significant differences between those treated with beta blockers and those not treated in the composite rate of death, recurrent heart attack, or heart-failure hospitalization. These neutral results call into question routine beta-blocker use for patients with preserved LVEF after an uncomplicated myocardial infarction.
Key subgroup result: sex-specific safety signal
A companion substudy published alongside the main REBOOT report found a clinically relevant sex difference. Women assigned to beta blockers had a higher absolute mortality risk (about 2.7 percentage points higher over the follow-up period) compared with women who did not receive beta blockers. This elevated risk was observed specifically in women whose ventricular function was completely normal (LVEF ≥ 50%). Men did not show the same increase in adverse outcomes.
Context: why practice may need to change
Historically, beta blockers were adopted after heart attacks because early trials — conducted when reperfusion strategies and adjunctive therapies were limited — showed mortality benefits. Beta blockers reduce myocardial oxygen demand and lower the risk of lethal arrhythmias. But acute cardiac care has advanced substantially: rapid coronary reperfusion, wider use of statins, ACE inhibitors/ARBs/ARNIs, antiplatelet therapy, and contemporary secondary-prevention strategies have reduced infarct size and arrhythmic risk.
"Therapies have evolved, and the absolute benefit previously attributed to beta blockers may no longer apply to patients whose hearts recover with preserved function," said Borja Ibáñez, MD, who presented the REBOOT results. “When the extent of myocardial damage is small, adding therapy that confers no added benefit — and carries side effects — deserves reconsideration.”
Safety, side effects and treatment burden
Beta blockers are generally regarded as safe but are associated with adverse effects that can impair quality of life, including fatigue, bradycardia (slow heart rate), exercise intolerance, and sexual dysfunction. Many post-MI patients already take multiple medications, so eliminating unnecessary drugs can simplify regimens, improve adherence, and reduce side effects.
The REBOOT investigators emphasized that the trial targeted patients with uncomplicated myocardial infarction and preserved LVEF. Patients with reduced ejection fraction, symptomatic heart failure, or other indications for beta blockers were not the primary population studied; existing evidence continues to support beta-blocker benefits in those contexts.
Implications for guidelines and clinical practice
Principal investigators and participating institutions, including the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and collaborators at Mount Sinai and the Mario Negri Institute, argue the data are robust enough to prompt revisions to guideline recommendations for post-MI care in patients with preserved ventricular function. REBOOT joins recent landmark trials — such as SECURE (polypill strategies) and DapaTAVI (SGLT2 inhibitors in valve disease) — that have also informed updates to cardiovascular practice.
If guideline committees adopt REBOOT findings, clinicians may stop prescribing beta blockers routinely to patients who recover normal ejection fraction after an uncomplicated heart attack, reserving the drugs for those with clear indications such as reduced LVEF or symptomatic arrhythmias.
Expert Insight
Dr. Maya Thompson, a clinical pharmacologist and cardiovascular researcher (fictional), comments: "REBOOT is an important example of revisiting entrenched practices in light of modern care. We must balance historical data with contemporary outcomes. Eliminating unnecessary therapy can reduce side effects and focus resources on interventions with proven incremental benefit. However, clinicians should individualize decisions — some patients may still derive benefit from beta blockers depending on arrhythmic risk, comorbidities, or LVEF deterioration over time."
Next steps and future research
Regulatory bodies and professional societies will review the REBOOT data to determine whether guideline statements should be updated. Additional research may explore mechanisms for the sex-specific signal, pharmacokinetic differences, or interactions with other post-MI therapies. Long-term registries could also monitor outcomes as changes in prescribing practice are implemented.
Conclusion
The REBOOT trial challenges a long-standing paradigm by demonstrating no overall clinical benefit from routine beta-blocker therapy after uncomplicated myocardial infarction in patients with preserved left ventricular function, and it raises safety concerns for women in this subgroup. These findings support re-evaluating discharge prescriptions to avoid unnecessary medications and underscore the need for updated guidance that reflects contemporary acute cardiovascular care.
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