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J Manag Care Pharm. 2011 Nov;17(9):672-84.

All-cause and bleeding-related health care costs in warfarin-treated patients with atrial fibrillation.

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Pharmacotherapy Outcomes ResearchCenter, University of Utah, 30 South 2000 East, Rm. 258, Salt Lake City, UT 84112-5820, USA.



Bleeding is a major complication of warfarin therapy. Assessing the cost of warfarin-associated bleeding may more fully describe the costs associated with warfarin use.


To assess health care costs related to warfarin-associated bleeding in patients with newly diagnosed atrial fibrillation (AF).


Medical and pharmacy claims were analyzed for patients with AF (ICD-9-CM code 427.31) in the Medstat MarketScan database from January 2003 to December 2007. Eligible patients had no warfarin pharmacy claim or AF diagnosis in the 4 months prior to AF index date, a warfarin pharmacy claim within 30 days of AF diagnosis, and 12 months follow-up data after the index warfarin claim. Subjects were categorized based on the first type of bleeding event observed during follow-up, and only bleeding events occurring within 30 days following a warfarin claim were considered. Intracranial hemorrhage (ICH) and gastrointestinal (GI) events were assessed based on primary or secondary ICD-9-CM codes, and major GI bleeding was defined as a GI bleed associated with hospitalization. Annual total all-cause allowed charges in patients with and without bleeding events after the index warfarin claim were compared using generalized linear model (GLM) regression with gamma distribution and log link, controlling for demographics, insurance status, and comorbidities. Costs for claims with a primary or secondary diagnosis of bleeding were calculated separately.


Of the 47,437 patients who were analyzed, 194 (0.4%) had an ICH, 919 (1.9%) had a major GI bleed, and 1,804 (3.8%) had a minor GI bleed within 30 days after a warfarin claim during follow-up. Compared with patients who had no bleeding events after a warfarin claim (n = 44,520, 93.9%) during the study period, patients with at least 1 bleeding event were older and had more comorbidities (P < 0.01). Patients with at least 1 ICH or major GI bleed had more all-cause hospitalizations (P < 0.05) and hospital days (P < 0.01) than patients without bleeding events. Patients with at least 1 ICH, major GI bleed, or minor GI bleed had more all-cause emergency room visits (P < 0.01) than patients without bleeding events. Mean (SD) unadjusted all-cause health care costs in the 12 months after the warfarin index claim were $41,903 ($56,654), $40,586 ($65,164), and $24,347 ($56,488) for patients with at least 1 ICH, major GI bleed, and minor GI bleed, respectively, compared with $24,129 ($36,425) for patients with no bleeding events. Claims with a primary or secondary diagnosis of bleeding accounted for 49.6%, 30.2%, and 2.6% of annual cost in patients with ICH, major GI bleeding, and minor GI bleeding, respectively. On average, 50.9%, 33.5%, and 10.8% of annual all-cause costs occurred within 30 days after the first ICH, major GI bleeding event, and minor GI bleeding event, respectively. GLM regression showed that annual all-cause costs were 64.4% and 49.0% higher (P? less than ?0.001) for patients with ICH and major GI bleeding, respectively, than for patients with no bleeding events.


ICH and major GI bleeding associated with warfarin therapy are rare but costly.

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