{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:20:27Z","timestamp":1791908427898,"version":"4.3.4"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2024,3,19]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>The efficacy and safety of non\u2013vitamin-K antagonist oral anticoagulants (NOACs) across the spectrum of body mass index (BMI) and body weight (BW) remain uncertain.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              We analyzed data from COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation), which pooled patient-level data from the 4 pivotal randomized trials of NOAC versus warfarin in patients with atrial fibrillation. The primary efficacy and safety outcomes were stroke or systemic embolic events (stroke\/SEE) and major bleeding, respectively; secondary outcomes were ischemic stroke\/SEE, intracranial hemorrhage, death, and the net clinical outcome (stroke\/SEE, major bleeding, or death). Each outcome was examined across BMI and BW. Because few patients had a BMI &lt;18.5 kg\/m\n              <jats:sup>2<\/jats:sup>\n              (n=598), the primary analyses were restricted to those with a BMI \u226518.5 kg\/m\n              <jats:sup>2<\/jats:sup>\n              .\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Among 58\u2009464 patients, the median BMI was 28.3 (interquartile range, 25.2\u201332.2) kg\/m\n              <jats:sup>2<\/jats:sup>\n              , and the median BW was 81.0 (interquartile range, 70.0\u201394.3) kg. The event probability of stroke\/SEE was lower at a higher BMI irrespective of treatment, whereas the probability of major bleeding was lower at a higher BMI with warfarin but relatively unchanged across BMI with NOACs. NOACs reduced stroke\/SEE overall (adjusted hazard ratio [HR\n              <jats:sub>adj<\/jats:sub>\n              ], 0.80 [95% CI, 0.73\u20130.88];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001), with a generally consistent effect across BMI (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              <jats:sub>trend<\/jats:sub>\n              across HRs, 0.48). NOACs also reduced major bleeding overall (HR\n              <jats:sub>adj<\/jats:sub>\n              , 0.88 [95% CI, 0.82\u20130.94];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001), but with attenuation of the benefit at a higher BMI (trend test across BMI [\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              <jats:sub>trend<\/jats:sub>\n              ], 0.003). The overall treatment effects of NOACs versus warfarin for secondary outcomes were consistent across BMI, with the exception of the net clinical outcome and death. While these outcomes were overall reduced with NOACs (net clinical outcome, HR\n              <jats:sub>adj<\/jats:sub>\n              , 0.91 [95% CI, 0.87\u20130.95];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001; death, HR\n              <jats:sub>adj<\/jats:sub>\n              , 0.91 [95% CI, 0.86\u20130.97];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.003), these benefits were attenuated at higher BMI (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              <jats:sub>trend<\/jats:sub>\n              , 0.001 and 0.08, respectively). All findings were qualitatively similar when analyzed across BW.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>The treatment effect of NOACs versus warfarin in atrial fibrillation is generally consistent for stroke\/SEE across the spectrum of BMI and BW, whereas the reduction in major bleeding is attenuated in those with higher BMI or BW. Death and the net clinical outcome are overall reduced with NOACs over warfarin, although there remain uncertainties for these outcomes at a very high BMI and BW.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.123.066279","type":"journal-article","created":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T05:00:31Z","timestamp":1706072431000},"page":"932-943","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["Efficacy and Safety of Non\u2013Vitamin-K Antagonist Oral Anticoagulants Versus Warfarin Across the Spectrum of Body Mass Index and Body Weight: An Individual Patient Data Meta-Analysis of 4 Randomized Clinical Trials of Patients With Atrial Fibrillation"],"prefix":"10.1161","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4637-4361","authenticated-orcid":true,"given":"Siddharth M.","family":"Patel","sequence":"first","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (S.M.P., E.B., M.G.P., E.M.A., E.A.B., D.A.M., C.T.R., R.P.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3472-626X","authenticated-orcid":true,"given":"Eugene","family":"Braunwald","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (S.M.P., E.B., M.G.P., E.M.A., E.A.B., D.A.M., C.T.R., R.P.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1477-9153","authenticated-orcid":true,"given":"Jan","family":"Steffel","sequence":"additional","affiliation":[{"name":"Hirslanden Clinic, Zurich, Switzerland and University of Zurich, Switzerland (J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9820-4815","authenticated-orcid":true,"given":"Giuseppe","family":"Boriani","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Policlinico di Modena, Italy (G.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2128-6752","authenticated-orcid":true,"given":"Michael G.","family":"Palazzolo","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (S.M.P., E.B., M.G.P., E.M.A., E.A.B., D.A.M., C.T.R., R.P.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0808-9199","authenticated-orcid":true,"given":"Elliott M.","family":"Antman","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (S.M.P., E.B., M.G.P., E.M.A., E.A.B., D.A.M., C.T.R., R.P.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5559-8172","authenticated-orcid":true,"given":"Erin A.","family":"Bohula","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (S.M.P., E.B., M.G.P., E.M.A., E.A.B., D.A.M., C.T.R., R.P.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9805-4562","authenticated-orcid":true,"given":"Anthony P.","family":"Carnicelli","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Internal Medicine, Medical University of South Carolina, Charleston 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(B.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0045-3291","authenticated-orcid":true,"given":"Christopher B.","family":"Granger","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Division of Cardiology, Duke University, Durham, NC (C.B.G., M.R.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9589-5382","authenticated-orcid":true,"given":"David A.","family":"Morrow","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (S.M.P., E.B., M.G.P., E.M.A., E.A.B., D.A.M., C.T.R., R.P.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2393-0855","authenticated-orcid":true,"given":"Manesh R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Division of Cardiology, Duke University, Durham, NC (C.B.G., M.R.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0378-6531","authenticated-orcid":true,"given":"Lars","family":"Wallentin","sequence":"additional","affiliation":[{"name":"Uppsala Clinical Research Center and Department of Medical Sciences, Uppsala University, Sweden (L.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4712-3206","authenticated-orcid":true,"given":"Christian T.","family":"Ruff","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (S.M.P., E.B., M.G.P., E.M.A., E.A.B., D.A.M., C.T.R., R.P.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4110-7675","authenticated-orcid":true,"given":"Robert 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