Summary

Although drug interactions with warfarin are an importantcause of excessive anticoagulation, their impact on the risk ofserious bleeding is unknown.We therefore performed a cohortstudy and a nested case-control analysis to determine the risk ofserious bleeding in 4152 patients (aged 40–84 years) with nonvalvularatrial fibrillation (AF) taking long-term warfarin (>3months).The study population was drawn from the UK GeneralPractice Research Database. More than half (58%) of eligible patientsused potentially interacting drugs during continuous warfarintreatment. Among 45 identified cases of incident idiopathicbleeds (resulting in hospitalisation within 30 days or death within7 days) and 143 matched controls, more cases than controlstook = 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 logisticregression analysis yielded an odds ratio (OR) of 3.4 (95%confidence interval [CI]: 1.4–8.5) for the risk of serious bleedingin patients treated with warfarin and = 1 drugs potentially increasingthe effect of warfarin vs. warfarin alone adjusted forpolypharmacy, diabetes, hypertension, heart failure, and thyroiddisease; the adjusted OR for the combined use of warfarin andaspirin vs. warfarin alone was 4.5 (95% CI: 1.1–18.1). We concludethat concurrent use of potentially interacting drugs withwarfarin is associated with a 3 to 4.5-fold increased risk of seriousbleeding in long-term warfarin users.