{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T16:23:12Z","timestamp":1778084592732,"version":"3.51.4"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,7,19]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Diltiazem, a moderate cytochrome P450 3A4 isozyme\/P\u2010glycoprotein inhibitor, may potentiate the bleeding risk of direct oral anticoagulants (DOACs) through pharmacokinetic interactions. We evaluated the association between concomitant use of diltiazem with DOACs and bleeding among patients with atrial fibrillation, across varying degrees of kidney function.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We identified 4544 patients with atrial fibrillation who were initiated on rivaroxaban (n=1583), apixaban (n=2373), or dabigatran (n=588), between 2010 and 2019 in Geisinger Health, with a mean age of 72\u2009years and an estimated glomerular filtration rate of 70\u2009mL\/min per 1.73\u2009m\n              <jats:sup>2<\/jats:sup>\n              . At the time of DOAC initiation, 15% patients were taking diltiazem and an additional 5% were initiated on diltiazem during follow\u2010up. Among DOAC users, using diltiazem concurrently (versus DOAC alone) was associated with an increased risk of any bleeding\u2010related hospitalization (unadjusted risk difference, 2.4; 95% CI, 0.6\u20134.2 events per 100 person\u2010years; adjusted hazard ratio, 1.56, 95% CI, 1.15\u20132.12), as well as major bleeding (unadjusted risk difference, 1.4 [95% CI, 0.1\u20132.6 events per 100 person\u2010years]; adjusted hazard ratio, 1.84 [95% CI, 1.18\u20132.85]). Increased risk of any\/major bleeding with diltiazem was observed in both patients with and without CKD (estimated glomerular filtration rate &lt;60\u2009mL\/min per 1.73\u2009m\n              <jats:sup>2<\/jats:sup>\n              ) (\n              <jats:italic>P<\/jats:italic>\n              for interaction=0.524 and 0.629, respectively). Among 13\u2009179 warfarin users (the negative control), concomitant diltiazem use was not associated with bleeding.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Concomitant use of diltiazem with DOACs was associated with a higher bleeding risk in patients with atrial fibrillation, consistently in both subgroups of chronic kidney disease and non\u2013chronic kidney disease. For DOAC users, concomitant diltiazem should be prescribed only when the benefit outweighs the risk, with close monitoring for signs of bleeding.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.025723","type":"journal-article","created":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T11:18:47Z","timestamp":1657019927000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Concomitant Use of Diltiazem With Direct Oral Anticoagulants and Bleeding Risk in Atrial Fibrillation"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5946-2272","authenticated-orcid":false,"given":"Yunwen","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex R.","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Nephrology Geisinger Health System Danville PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2820-9482","authenticated-orcid":false,"given":"Lesley A.","family":"Inker","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine Tufts Medical Center Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara","family":"McAdams\u2010DeMarco","sequence":"additional","affiliation":[{"name":"Department of Surgery New York University Grossman School of Medicine and Langone Health New York NY"},{"name":"Department of Population Health New York University Grossman School of Medicine and Langone Health New York NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4430-6023","authenticated-orcid":false,"given":"Morgan E.","family":"Grams","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD"},{"name":"Department of Population Health New York University Grossman School of Medicine and Langone Health New York NY"},{"name":"Department of Medicine New York University Grossman School of Medicine and Langone Health New York NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0374-6927","authenticated-orcid":false,"given":"Jung\u2010Im","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","article-title":"Chronic kidney disease and atrial fibrillation: a contemporary overview","volume":"5","author":"Kulkarni N","year":"2012","unstructured":"Kulkarni N, Gukathasan N, Sartori S, Baber U. 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