A groundbreaking clinical trial led by Valentin Fuster, MD, PhD, has delivered a pivotal challenge to the long-standing standard treatment for heart attack patients involving beta blockers. Known for their decades-long use following myocardial infarction, beta blockers have now been shown to provide no clinical benefit for individuals who have experienced an uncomplicated heart attack with preserved cardiac function. This landmark discovery emerges from the REBOOT Trial, a large-scale international randomized controlled study coordinated by the Centro Nacional de Investigaciones Cardiovasculares (CNIC) in Spain, in collaboration with Italy’s Mario Negri Institute for Pharmacological Research.
For over 40 years, beta blockers have been routinely prescribed to patients post-myocardial infarction to reduce mortality risks through their mechanisms of lowering heart rate, oxygen demand, and preventing arrhythmias. However, advancements in reperfusion therapies and standard care have transformed the clinical landscape, necessitating a reassessment of the benefits attributed to these drugs within a modern therapeutic context. The REBOOT Trial rigorously evaluated the impact of discontinuing beta blockers in patients with normal left ventricular function, a subgroup that had not been extensively studied under contemporary treatment protocols.
The trial enrolled 8,505 patients across 109 hospitals in Spain and Italy, randomly assigning participants to either continue or cease beta blocker treatment after discharge. All patients otherwise received state-of-the-art care, including prompt coronary artery reperfusion and modern pharmacotherapies. Over a median follow-up period of almost four years, the primary endpoints—rates of death, recurrent myocardial infarction, and hospitalization for heart failure—showed no statistically significant difference between the beta blocker and non-beta blocker groups. These results strongly suggest that beta blockers may no longer confer the protective benefits once assumed in this patient population.
A particularly illuminating aspect of the REBOOT substudy was its gender-specific analysis, which revealed concerning findings for female patients. Women treated with beta blockers exhibited a 2.7 percent higher absolute risk of adverse outcomes—including death, subsequent heart attacks, and heart failure hospitalization—compared to untreated women with preserved cardiac function. Conversely, men receiving beta blockers did not experience this increased risk. This sex-specific distinction underscores the importance of personalized medicine and calls for further exploration into the molecular and physiological mechanisms underlying these differences.
Scientific understanding posits that beta blockers improve outcomes primarily by reducing cardiac workload and suppressing arrhythmogenic risk immediately after myocardial injury. Yet, contemporary treatment approaches emphasize rapid restoration of coronary artery patency through percutaneous interventions, effectively minimizing ischemic damage. This evolution leads to less residual myocardial impairment and may diminish the therapeutic necessity of beta blockers, especially in patients without reduced left ventricular ejection fraction. The thorough design of REBOOT reflects this hypothesis, aiming to update clinical practices based on robust evidence rather than tradition.
Dr. Borja Ibáñez, the trial’s principal investigator and CNIC Scientific Director, emphasizes the transformative potential of the findings. Highlighting that currently over 80 percent of patients with uncomplicated myocardial infarction are prescribed beta blockers at discharge, he suggests these results will prompt significant revisions in international guidelines. The implications extend beyond clinical efficacy to patient quality of life, considering beta blockers’ known side effects such as fatigue, bradycardia, and sexual dysfunction. Streamlining post-infarct medication regimens could enhance adherence and reduce needless exposure to drug-related adverse events.
The REBOOT Trial joins an influential cohort of cardiovascular studies spearheaded by CNIC and Mount Sinai institutions, each shifting paradigms in heart disease management. Previous landmark trials include the SECURE study, which demonstrated that a polypill combining aspirin, ramipril, and atorvastatin significantly lowers cardiovascular events, and the DapaTAVI trial, which showed benefits of sodium-glucose cotransporter 2 inhibitors in patients undergoing transcatheter aortic valve implantation. Together, these studies illustrate a profound evolution in understanding and optimizing cardiovascular care with precision medicine.
From a methodological standpoint, the REBOOT Trial’s randomized controlled design, extensive sample size, and multicenter collaboration provide a robust framework for drawing conclusive evidence. The absence of pharmaceutical industry funding further strengthens the trial’s credibility, ensuring findings are free of commercial bias. The integration of sophisticated subgroup analyses enriches insights into patient stratification, particularly regarding sex differences and cardiac function parameters, a level of granularity uncommon in large-scale cardiovascular trials.
The trial’s findings echo an emerging trend in contemporary cardiology that questions the indiscriminate continuation of historical treatments without reassessing their roles amid advances in therapeutic intervention and diagnostics. Modern reperfusion therapy has substantially mitigated the extent and consequence of myocardial injury, thus recalibrating the risk-benefit analysis of adjunctive medications. In this light, beta blockers appear less vital for patients with preserved ventricular function, whereas their use may remain justified in those with impaired cardiac output.
Another critical consideration arising from REBOOT is the enhanced understanding of sex-specific responses to cardiovascular medications. The data indicating elevated adverse outcomes in women prescribed beta blockers prompts a re-evaluation of gender inclusivity in clinical trials and therapeutic approaches. Differentiation in drug metabolism, hormonal influences, and genetic determinants may all contribute to this phenomenon, signaling a broader imperative for tailored, individualized treatment algorithms.
The clinical community awaits further analyses and guideline updates to incorporate these findings into routine practice. Meanwhile, the results invite clinicians to critically appraise the necessity of beta blockers in patients after uncomplicated myocardial infarction, especially those whose cardiac function remains robust. This nuanced approach could refine risk stratification and therapeutic decision-making, ultimately improving patient outcomes and quality of life.
In summary, the REBOOT Trial represents a seismic shift in cardiology, overturning a four-decade-old dogma around beta blocker use post-myocardial infarction with preserved ejection fraction. The study exemplifies the critical need for ongoing appraisal of legacy treatments under the lens of contemporary evidence and underscores the dynamic nature of medical practice guided by rigorous scientific inquiry. As cardiac care continues to evolve, these insights pave the way towards more effective, personalized, and patient-centered medicine.
Subject of Research: People
Article Title: Beta-Blockers after Myocardial Infarction without Reduced Ejection Fraction
News Publication Date: 30-Aug-2025
Image Credits: Mount Sinai Health System
Keywords: Cardiovascular disorders, Clinical trials, Drug studies, Medical treatments, Drug delivery, Drug therapy
