title: Drug interactions and risk of acute bleeding leading to hospitalisation or death in patients with chronic atrial fibrillation treated with warfarin.
abstract: Although drug interactions with warfarin are an important cause of excessive anticoagulation, their impact on the risk of serious bleeding is unknown. We therefore performed a cohort study and a nested case-control analysis to determine the risk of serious bleeding in 4152 patients (aged 40-84 years) with nonvalvular atrial fibrillation (AF) taking long-term warfarin (> 3 months). The study population was drawn from the UK General Practice Research Database. More than half (58%) of eligible patients used potentially interacting drugs during continuous warfarin treatment. Among 45 identified cases of incident idiopathic bleeds (resulting in hospitalisation within 30 days or death within 7 days) and 143 matched controls, more cases than controls took > or = 1 potentially interacting drug within the preceding 30 days (62.2% vs. 35.7%) and used > 4 drugs (polypharmacy) within the preceding 90 days (80.0% vs. 66.4%). Conditional logistic regression analysis yielded an odds ratio (OR) of 3.4 (95% confidence interval [CI]: 1.4-8.5) for the risk of serious bleeding in patients treated with warfarin and > or = 1 drugs potentially increasing the effect of warfarin vs. warfarin alone adjusted for polypharmacy, diabetes, hypertension, heart failure, and thyroid disease; the adjusted OR for the combined use of warfarin and aspirin vs. warfarin alone was 4.5 (95% CI: 1.1-18.1). We conclude that concurrent use of potentially interacting drugs with warfarin is associated with a 3 to 4.5-fold increased risk of serious bleeding in long-term warfarin users.
authors.affiliation: Department of Internal MedicineVI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Germany. Christiane.gasse@med.uni-heidelberg.de
authors.forename: Christiane
authors.initials: C
authors.lastname: Gasse
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hollowell
authors.forename: Christoph R
authors.initials: CR
authors.lastname: Meier
authors.forename: Walter E
authors.initials: WE
authors.lastname: Haefeli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D016022:Case-Control Studies; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000517:prevention & control*; D002908:Chronic Disease; D004347:Drug Interactions; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology*; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D015912:Thrombolytic Therapy; D006113:United Kingdom; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018712:Analgesics, Non-Narcotic; D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D014859:Warfarin