Pharmaceutical economics & health policy Original research| Volume 34, ISSUE 7, P1569-1582, July 2012

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Risk of Hemorrhage and Treatment Costs Associated With Warfarin Drug Interactions in Patients With Atrial Fibrillation



      Drug interactions with warfarin are common and may be responsible for increased patient morbidity and treatment costs.


      To assess the usage patterns of drugs that potentiate warfarin's anticoagulant activity and discuss their associated relationship with both risk of hemorrhage and treatment costs among warfarin users with atrial fibrillation (AF).


      A nested case–control study of long-term warfarin-treated AF patients was conducted using a health insurance claims database. Patients with a hemorrhagic event (cases) were matched to control patients using the incidence density sampling method. Drug-potentiating warfarin effects were identified within 30 days before the hemorrhagic event. Conditional logistic regression was used to calculate the association between use of potentiating drugs and hemorrhage risk. Mean treatment costs and CIs were calculated using the bootstrap method and tested using the t-test. Factors associated with treatment costs were determined using generalized linear models with the log-link function and γ distribution.


      Approximately 80% of AF patients were prescribed at least 1 warfarin-potentiating medication while taking warfarin. Patients who used these medications had a 26% higher risk of hemorrhage compared with those who did not use these drugs. Likelihood of hemorrhagic events was significantly increased with the use of potentiating drugs from the following therapeutic classes: anticoagulants (odds ratio [OR] = 1.91), anti-infectives (OR = 1.76), antiplatelets (OR = 1.56), and analgesics (OR = 1.33). The risk also increased when patients took ≥3 therapeutic classes of interacting medications (OR = 1.62–1.85). Among patients with a hemorrhagic event, patients who were prescribed potentiating drugs had higher hemorrhage-related treatment costs ($1359) compared with those patients without prescriptions for warfarin-potentiating drugs ($691; P < 0.001).


      Warfarin-potentiating drugs were commonly used among AF patients on warfarin. The use of potentiating drugs increased the risk of a hemorrhage, leading to higher treatment costs. More frequent monitoring or alternative anticoagulant therapies are needed to avoid frequent warfarin drug interactions.


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