Two major international trials presented simultaneously at the European Society of Cardiology Congress have delivered conflicting results on beta-blocker therapy after heart attacks, creating unprecedented uncertainty about a treatment that has been standard care for four decades.
The BETAMI-DANBLOCK combined trials, involving 5,574 patients from Norway and Denmark, demonstrated a significant 15% reduction in cardiovascular events among heart attack patients with preserved or mildly reduced left ventricular ejection fraction (LVEF ≥40%) who received beta-blockers compared to those who did not. After a median follow-up of 3.5 years, the primary composite endpoint of all-cause mortality and major adverse cardiovascular events occurred in 14.2% of beta-blocker patients versus 16.3% in the control group (hazard ratio 0.85; 95% CI 0.75 to 0.98; p=0.027).
Contradictory Evidence Emerges
In stark contrast, the REBOOT trial—the largest study of its kind involving 8,505 patients across 109 hospitals in Spain and Italy—found no clinical benefit from beta-blockers in patients with uncomplicated myocardial infarction and preserved heart function. After nearly four years of follow-up, researchers observed no significant differences between beta-blocker and control groups in rates of death, recurrent heart attack, or hospitalization for heart failure.
"REBOOT will change clinical practice worldwide," stated Principal Investigator Dr. Borja Ibáñez, CNIC's Scientific Director. "Currently, more than 80 percent of patients with uncomplicated myocardial infarction are discharged on beta blockers. The REBOOT findings represent one of the most significant advances in heart attack treatment in decades."
Gender-Specific Safety Concerns
The REBOOT trial revealed a particularly troubling finding for women. A subgroup analysis published in the European Heart Journal showed that women treated with beta-blockers experienced a 2.7% higher absolute risk of mortality compared to untreated women during the 3.7-year follow-up period. This elevated risk was specifically observed in women with completely normal cardiac function (LVEF ≥50%) after their heart attack, while men showed no such increased risk.
Clinical Context and Implications
The conflicting results highlight the complexity of evaluating established therapies in the context of modern cardiac care. As Professor Dan Atar from Oslo University Hospital explained, "Evidence supporting beta-blocker therapy after MI was established before the introduction of modern coronary reperfusion therapy and secondary prevention strategies."
Dr. Ibáñez emphasized the evolution of heart attack treatment: "Today, occluded coronary arteries are reopened rapidly and systematically, drastically lowering the risk of serious complications such as arrhythmias. In this new context—where the extent of heart damage is smaller—the need for beta blockers is unclear."
Study Populations and Methodology
The BETAMI-DANBLOCK trials enrolled patients within 7-14 days of myocardial infarction if they had LVEF ≥40% and no clinical heart failure diagnosis. The median age was 63 years, with 20.8% being women. Only 10.5% had a history of coronary artery disease, and 8.4% were on beta-blocker treatment prior to enrollment.
In the BETAMI-DANBLOCK analysis, new myocardial infarction occurred in 5.0% of beta-blocker patients versus 6.7% of control patients (HR 0.73; 95% CI 0.59 to 0.92), representing a notable reduction in recurrent events.
Future Clinical Practice
Professor Eva Prescott from Copenhagen University Hospital noted that "the results must be considered alongside other recent and ongoing trials of beta-blocker therapy after MI to determine their implications for clinical practice."
Senior investigator Dr. Valentin Fuster, President of Mount Sinai Fuster Heart Hospital, emphasized the broader impact: "This trial will reshape all international clinical guidelines. It joins other previous landmark trials led by CNIC and Mount Sinai that have already transformed some global approaches to cardiovascular disease."
The contradictory findings from these well-designed trials underscore the need for careful consideration of patient-specific factors, including gender and cardiac function status, when making treatment decisions about beta-blocker therapy following myocardial infarction.
