In a groundbreaking meta-analysis conducted by the Centro Nacional de Investigaciones Cardiovasculares (CNIC) alongside an international consortium of researchers, long-standing clinical assumptions about the use of beta-blockers following myocardial infarction (MI) have been decisively challenged. This comprehensive study aggregated individual patient data from five major contemporary clinical trials encompassing 17,801 survivors of myocardial infarction who maintained preserved left ventricular function, defined as a left ventricular ejection fraction (LVEF) equal to or above 50%. The outcome unequivocally indicates that beta-blocker therapy confers no significant clinical benefit regarding mortality reduction, prevention of recurrent infarction, or the avoidance of heart failure in this predominant patient population.
Beta-blockers have been a cornerstone of post-MI management for over four decades, primarily based on evidence from clinical trials conducted in the 1970s and 1980s, which demonstrated a survival benefit in a broad cohort of infarction patients. However, revolutionary advances in acute coronary care—including rapid reperfusion strategies, robust antithrombotic regimens, and optimized secondary prevention—have profoundly altered the risk profile and clinical course of these patients. Consequently, it became imperative to reassess the therapeutic value of beta-blockers in the current era, especially in patients exhibiting preserved cardiac contractility.
The meta-analysis integrated datasets from the REBOOT, REDUCE-AMI, BETAMI, DANBLOCK, and CAPITAL-RCT trials conducted across diverse geographic regions including Spain, Italy, Sweden, Norway, Denmark, and Japan. This multinational collaboration facilitated a granular and robust evaluation of beta-blocker efficacy by encompassing variations in patient demographics, beta-blocker types, and treatment protocols. Approximately half of the participants received beta-blockers, while the other half did not, allowing for head-to-head comparison over an average follow-up approaching four years. The incidence of major cardiovascular events—a composite endpoint of all-cause mortality, recurrent MI, or heart failure hospitalization—was statistically indistinguishable between treatment arms.
Dr. Borja Ibáñez, CNIC Scientific Director and principal investigator, emphasized that subgroup analyses failed to reveal any differential benefit across age, sex, or beta-blocker subclass. Intriguingly, prior signals from the REBOOT trial hinted at potential harm in female patients receiving beta-blockers post-MI, a concern the meta-analysis sought to clarify. While women showed a trend toward increased adverse events under beta-blocker therapy, this observation did not reach statistical significance, underscoring the need for ongoing evaluation of sex-specific treatment responses in cardiovascular medicine.
Importantly, the study delineates the clinical context where beta-blockers retain their indispensable role. Patients with reduced LVEF (<50%) post-MI, as well as those with chronic heart failure or arrhythmias, continue to derive clear mortality and morbidity reduction from beta-blocker therapy. The trials analyzed intentionally excluded patients already on beta-blockers for these indications, ensuring the findings apply strictly to initiating beta-blocker therapy in infarction survivors with normal ejection fraction. This distinction is critical in guiding personalized treatment algorithms and avoiding unnecessary medication burden.
The implications of these findings are profound given that approximately 70% of contemporary MI survivors now present with preserved cardiac function—an epidemiological shift attributed to improved acute management and secondary prevention. This paradigm shift fundamentally questions the universal prescription of beta-blockers, urging a tailored approach based on cardiac function assessment. Dr. Valentín Fuster, General Director at CNIC and a global authority on cardiovascular medicine, remarked that this meta-analysis conclusively overturns treatment dogma that has remained largely unquestioned for more than 40 years, heralding a new standard of care that could substantially refine patient management worldwide.
In practical terms, this evolution reduces exposure to potential beta-blocker-associated side effects, including fatigue and sexual dysfunction, thereby improving long-term quality of life for millions of patients. The investigators caution against abrupt discontinuation of beta-blockers without clinical consultation, as the decision must consider individual patient indications beyond MI treatment. Physicians are encouraged to assess beta-blocker necessity during routine follow-ups and discontinue therapy judiciously in patients with preserved ejection fraction who lack alternate indications.
This meta-analysis also exemplifies the power of international scientific collaboration executed at unprecedented speed, enabling rapid synthesis of high-quality evidence to resolve contentious clinical questions. By harmonizing raw data across heterogeneous trials, the researchers achieved unparalleled statistical power and confidence in their conclusions. Such methodological rigor and collaboration serve as a model for future cardiovascular research, particularly in precision medicine initiatives targeting nuanced patient subgroups.
Furthermore, the CNIC’s commitment to investigating sex-based differences in cardiovascular treatment outcomes highlights an essential dimension of patient-centered care, seeking to optimize therapeutic efficacy and safety across diverse populations. This focus aligns with contemporary emphasis on equity and inclusiveness in clinical trials and guideline formulation.
As the clinical community digest this pivotal evidence, it is anticipated that international guidelines will be updated to reflect the limited role of beta-blockers in post-MI patients with preserved ventricular function. This transition heralds a more rational, evidence-based prescription approach, minimizing unnecessary pharmacotherapy while safeguarding patients with established indications.
In summary, this meta-analysis represents a milestone in cardiovascular therapeutics, conclusively demonstrating that beta-blockers do not reduce mortality, recurrent myocardial infarction, or heart failure in infarction survivors with normal cardiac function. The clinical narrative evolves toward stratified medicine, reserving beta-blocker therapy for patients with impaired ejection fraction or other validated indications. This paradigm shift will transform clinical practice globally, improving patient outcomes and quality of life while fostering more efficient resource utilization.
Subject of Research: People
Article Title: Beta-Blockers after Myocardial Infarction with Normal Ejection Fraction
News Publication Date: 9-Nov-2025
Web References: http://dx.doi.org/10.1056/NEJMoa2512686
Image Credits: CNIC
Keywords: Health and medicine, Human health, Medical specialties, Pharmacology, Pharmaceuticals, Epidemiology, Diseases and disorders, Clinical medicine
