{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:48:09Z","timestamp":1782283689162,"version":"3.54.5"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We aimed to evaluate the efficacy of \u03b2\u2010blockers after myocardial infarction (MI) across left ventricular ejection fraction (LVEF) strata and to assess the conclusiveness of the available evidence using trial sequential analysis (TSA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      PubMed, Embase and\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      were searched for randomized controlled trials (RCTs) evaluating \u03b2\u2010blockers in post\u2010MI patients with LVEF\u2009\u2265\u200940%. A time\u2010to\u2010event meta\u2010analysis was performed for the primary composite (as defined by each trial) and for individual endpoints. The Mantel\u2013Haenszel method was used to pool risk ratios (RR) for major adverse cardiovascular events (MACE; death, MI or heart failure), including LVEF\u2010stratified analyses. TSA estimated the required information size (RIS) and generated adjusted significance and futility boundaries, assuming a 5% type I error and 90% power.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Across 19,826 post\u2010MI patients (17,941 with LVEF\u2009\u2265\u200950% and 1885 with LVEF 40%\u201349%), \u03b2\u2010blockers did not reduce time to the primary endpoint (HR 0.92, 95% CI 0.85\u20131.01;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.08;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200935%) or mortality. In patients with preserved LVEF (\u2265\u200950%), \u03b2\u2010blocker therapy did not reduce the risk of death or MACE (RR 0.96, 95% CI 0.87\u20131.05;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200942%), with TSA confirming futility. Among those with mildly reduced LVEF (40%\u201349%), \u03b2\u2010blockers reduced MACE (RR 0.74, 95% CI 0.58\u20130.94;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090%), although TSA failed to establish conclusiveness (RIS of 5717 [14.4%]). A significant interaction by LVEF subgroup was observed for cardiac death (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\u03b2\u2010blockers conferred no benefit in post\u2010MI patients with preserved LVEF, with conclusive evidence of futility, whereas therapy was associated with reduced MACE in those with mildly reduced LVEF, pending confirmation in further adequately powered randomized trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/eci.70238","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:45:49Z","timestamp":1781757949000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beta\u2010Blockers After Myocardial Infarction With Preserved and Mildly Reduced Ejection Fraction: A Meta\u2010Analysis With Trial Sequential Analysis"],"prefix":"10.1111","volume":"56","author":[{"given":"Michele","family":"Maremmani","sequence":"first","affiliation":[{"name":"Department of Cardiology Sant'Andrea Hospital  La Spezia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Gianfico","sequence":"additional","affiliation":[{"name":"Department of Cardiology Vita\u2010Salute San Raffaele University  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Templin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine B University of Medicine Greifswald  Greifswald Germany"},{"name":"Center for Molecular Cardiology, Schlieren Campus University of Zurich  Zurich 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