Ibanez, BorjaLatini, RobertoRossello, XavierDominguez-Rodriguez, AlbertoFernández-Vazquez, FelipePelizzoni, ValentinaSánchez, Pedro LAnguita, ManuelBarrabés, José ARaposeiras-Roubín, SergioPocock, StuartEscalera, NoemíStaszewsky, LidiaPérez-García, Carlos NicolásDíez-Villanueva, PabloPérez-Rivera, Jose-AngelPrada-Delgado, OscarOwen, RuthPizarro, GonzaloCaldes, OnofreGómez-Talavera, SandraTuñón, JoséBianco, MatteoZarauza, JesusVetrano, AlfredoCampos, AnaMartínez-Huertas, SusanaBueno, HéctorPuentes, MiguelGrigis, GiuliettaBonilla-Palomas, Juan LMarco, ElviraGonzález-Juanatey, José RBangueses, RoiGonzález-Juanatey, CarlosGarcía-Álvarez, AnaRuiz-García, JuanCarrasquer, AnnaGarcía-Rubira, Juan CPascual-Figal, DomingoTomás-Querol, CarlosSan Román, J AlbertoBaratta, PasqualeAgüero, JaumeMartín-Reyes, RobertoColivicchi, FurioOrtas-Nadal, RosarioBazal, PabloCordero, AlbertoFernández-Ortiz, AntonioBasso, PierangeloGonzález, EvaPoletti, FabrizioBugani, GiuliaDebiasio, MarziaCosmi, DeborahNavazio, AlessandroBermejo, JavierTortorella, GiovanniMarini, MarcoBotas, Javierde la Torre-Hernández, José MOttani, FilippoFuster, Valentín2025-12-152025-12-152025-11-13N Engl J Med. 2025 Nov 13;393(19):1889-1900.https://hdl.handle.net/20.500.12105/27034Current guideline recommendations for the use of beta-blockers after myocardial infarction without reduced ejection fraction are based on trials conducted before routine reperfusion, invasive care, complete revascularization, and contemporary pharmacologic therapies became standard practice. We conducted an open-label, randomized trial in Spain and Italy to evaluate the effect of beta-blocker therapy, as compared with no beta-blocker therapy, in patients with acute myocardial infarction (with or without ST-segment elevation) and a left ventricular ejection fraction above 40%. The primary outcome was a composite of death from any cause, reinfarction, or hospitalization for heart failure. In total, 4243 patients were randomly assigned to receive beta-blocker therapy and 4262 to receive no beta-blocker therapy; after exclusions, 8438 patients were included in the main analysis. During a median follow-up of 3.7 years, a primary-outcome event occurred in 316 patients (22.5 events per 1000 patient-years) in the beta-blocker group and in 307 patients (21.7 events per 1000 patient-years) in the no-beta-blocker group (hazard ratio, 1.04; 95% confidence interval [CI], 0.89 to 1.22; P = 0.63). Death from any cause occurred in 161 patients and 153 patients, respectively (11.2 vs. 10.5 events per 1000 patient-years; hazard ratio, 1.06; 95% CI, 0.85 to 1.33); reinfarction in 143 patients and 143 patients (10.2 vs. 10.1 events per 1000 patient-years; hazard ratio, 1.01; 95% CI, 0.80 to 1.27); and hospitalization for heart failure in 39 patients and 44 patients (2.7 vs. 3.0 events per 1000 patient-years; hazard ratio, 0.89; 95% CI, 0.58 to 1.38). No apparent between-group differences in safety outcomes were noted. Among patients discharged after invasive care for a myocardial infarction with a left ventricular ejection fraction above 40%, beta-blocker therapy appeared to have no effect on the incidence of death from any cause, reinfarction, or hospitalization for heart failure. (Funded by Centro Nacional de Investigaciones Cardiovasculares Carlos III and others; ClinicalTrials.gov number, NCT03596385; EudraCT number, 2017-002485-40.).Funded by the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), the Swedish Research Council, The Swedish Heart and Lung Foundation, the Region of Stockholm, the South-Eastern Norway Regional Health Authority, the Research Council of Norway, the Danish Heart Foundation, the Novo Nordisk Foundation, and Research Institute for Production Development (Kyoto, Japan).engAMhttp://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 International40888702NEW ENGLAND JOURNAL OF MEDICINEopen access