{"id":21896,"date":"2025-05-28T09:28:14","date_gmt":"2025-05-28T13:28:14","guid":{"rendered":"https:\/\/www.ices.on.ca\/?post_type=journal_article&p=21896"},"modified":"2025-06-05T09:38:59","modified_gmt":"2025-06-05T13:38:59","slug":"association-of-direct-oral-anticoagulant-proton-pump-inhibitor-co-therapy-with-adverse-outcomes","status":"publish","type":"journal_article","link":"https:\/\/www.ices.on.ca\/fr\/publications\/journal-articles\/association-of-direct-oral-anticoagulant-proton-pump-inhibitor-co-therapy-with-adverse-outcomes\/","title":{"rendered":"Association of direct oral anticoagulant-proton pump inhibitor co-therapy with adverse outcomes: a population-based cohort study"},"content":{"rendered":"

Background<\/strong> \u2014 Direct-acting oral anticoagulants (DOACs) are first-line therapy for atrial fibrillation and for venous thromboembolism prevention and treatment. In addition, proton pump inhibitors (PPIs) are recommended by the ACC Expert Consensus for patients receiving DOAC.<\/p>\n

Objective<\/strong> \u2014 To determine the risk of clinically important thromboembolic and bleeding events and death in patients concomitantly prescribed DOACs and PPIs compared with DOAC alone.<\/p>\n

Methods<\/strong> \u2014 We undertook a population-based cohort study of Ontario residents aged 66 years or older who were newly dispensed a DOAC from 2009 to 2020. The primary outcome was a composite of clinically relevant bleeding, thrombotic events, and all-cause death. We then used a time-dependent Cox regression model to estimate the adjusted hazard of outcomes during time periods where patients were exposed vs not exposed to PPI.<\/p>\n

Results<\/strong> \u2014 We included 283\u2009771 new DOAC users (mean age 78.3 years, 49.4% female). The age\/sex-standardized outcome event rate of the composite outcome was higher in the DOAC-PPI cohort [20.2 (95% CI 20.0-20.5) per 100 person-years] than in the DOAC-alone cohort [15.2 (95% CI 15.1-15.4) per 100 person-years]. In time-dependent Cox regression analyses examining time periods during DOAC-PPI co-therapy vs DOAC alone, risks were elevated for all outcomes during periods of PPI co-therapy, suggesting residual confounding. In a secondary analysis of patients receiving DOAC-PPI co-therapy (n = 115\u2009493), periods of DOAC-PPI co-therapy were associated with a greater hazard for death (HR 2.24, 95% CI 2.14-2.35), but a lower risk for both thrombosis (HR 0.93, 95% CI 0.89-0.96) and clinically relevant bleeding (HR 0.79, 95% CI 0.76-0.81).<\/p>\n

Conclusion and relevance<\/strong> \u2014 Our cohort study of older adults suggests that DOAC-PPI co-therapy is associated with decreased upper GI bleeding but increased mortality. Since the implications are major and may be due to residual confounding, we recommend that the findings be verified in randomized trials before clinical application.<\/p>\n","protected":false},"excerpt":{"rendered":"

Background \u2014 Direct-acting oral anticoagulants (DOACs) are first-line therapy for atrial fibrillation and for venous thromboembolism prevention and treatment. In addition, proton pump inhibitors (PPIs) are recommended by the ACC Expert Consensus for patients receiving DOAC. Objective \u2014 To determine the risk of clinically important thromboembolic and bleeding events and death in patients concomitantly prescribed […]<\/p>\n","protected":false},"template":"","migration-helper-automated":[],"migration-manual":[],"topic":[17,56],"migration-helper-qa-sample-set":[],"class_list":["post-21896","journal_article","type-journal_article","status-publish","hentry","topic-older-people","topic-pharmacoepidemiology-and-drug-safety"],"acf":{"citation":"Wang M, Paterson JM, Nguyen F, Siegal DM, Targownik L, Holbrook AM. Ann Pharmacother<\/em>. 2025; May 28 [Epub ahead of print].","source_url":"https:\/\/doi.org\/10.1177\/10600280251337209","ices_scientist":[1100],"site":[6737],"research_program":[6746],"news_release":"","journal_article":"","atlas":"","research_report":"","infographic":"","video":"","downloads":null,"links":null,"sitecore_item_id":"","sitecore_item_name":"","sitecore_field_values":"","previous_url":""},"yoast_head":"\nICES | Association of direct oral anticoagulant-proton pump inhibitor co-therapy with adverse outcomes: a population-based cohort study<\/title>\n<meta name=\"description\" content=\"Background \u2014 Direct-acting oral anticoagulants (DOACs) are first-line therapy for atrial fibrillation and for venous thromboembolism prevention and\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" 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