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Anticoagulation Therapy for Patients with Non-Valvular Atrial Fibrillation

Comparison of Decision Analytic Model Recommendations and Real-World Warfarin Prescription Use

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Background: Anticoagulation in patients with atrial fibrillation (AF) is challenging because stroke-risk reduction must be balanced against increased bleeding risk.

Objective: We developed a decision model integrating both stroke and bleeding risk schemes to guide optimal use of anticoagulation in AF, and compared model recommendations with warfarin use in a real-world database.

Methods: A Markov model based on demographics, CHADS2 (Congestive Heart Failure, Hypertension, Age of 75 years and greater, Diabetes Mellitus and History of Stroke) stroke and ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleed risk scores, and anticoagulation treatment effects from clinical trials simulated health state transitions for recently diagnosed AF patients. The model recommended the treatment with greater quality-adjusted life expectancy. Model recommendations were contrasted with actual warfarin use recorded in the Thomson Reuters MarketScan database (N=64 946).

Results: 74.8% (n = 48 548) of the Marketscan AF cohort had CHADS2 ≥1, of whom 14.3% had moderate/high (≥4) ATRIA bleeding risk. While the model recommended warfarin for almost all patients with CHADS2 ≥1 who are at low bleeding risk, it recommended warfarin for fewer patients as bleeding risk increased. Of the 44 611 patients recommended warfarin, 63.4% of patients were considered warfarin exposed (concordant with model recommendation), and of the 20 335 patients recommended aspirin (ace-tylsalicylic acid), 59.7% received warfarin (discordant with model recommendations). Actual warfarin use decreased modestly with higher stroke risk (p< 0.0001) and with higher bleeding risk (p< 0.0001).

Conclusion: High discordance between actual warfarin use and model recommendations suggests that anticoagulation decisions are not based on systematic evaluation of stroke and bleeding risks. Model-based clinical decision aids may improve oral anticoagulation decisions by more systematically weighing bleed and stroke risk.

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The authors wish to thank Michael Hagan DPH, MA, for assistance with study design, analysis, and review; as well as Gary Moore, MS, University of Arkansas, USA, for help in preparing the analytic extracts from the MarketScan data. They would also like to acknowledge Richert E. Goyette, MD, in editing the manuscript for language accuracy, incorporating author comments, preparing and formatting the bibliography, and formatting tables and figures, which was supported by Daiichi Sankyo.

Funding sources: This study was funded by Daiichi Sankyo, Inc.

Relationship with industry: JPC is employed by eMAX Health Systems, LLC, and received consulting fees from Daiichi Sankyo to conduct the analysis; and is a consultant to Pfizer, Inc., manufacturer of a novel anticoagulant. DES received a research grant from Daiichi Sankyo, Inc., to develop a model of risk of bleeding for patients with atrial fibrillation taking anticoagulants. This grant ended in July 2010. Daiichi Sankyo, Inc., is developing a novel anticoagulant for use in patients with atrial fibrillation. DES is a consultant/advisory board member for Bayer HealthCare, manufacturer of a novel anticoagulant; Boehringer Ingelheim, manufacturer of a novel anticoagulant; Bristol-Myers Squibb, manufacturer of a novel anticoagulant; Daiichi Sankyo, Inc., manufacturer of a novel anticoagulant; Pfizer, Inc., a manufacturer of a novel anticoagulant; and Ortho-McNeil/Johnson & Johnson, Inc., manufacturer of a novel anticoagulant.

WJK and ESF are employees of Daiichi Sankyo, Inc.

BCM is a consultant to eMax Health and Daiichi Sankyo for studies related to the risks and benefits of oral anticoagulation and a consultant to Bayer for cost studies in pulmonary hypertension.

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Correspondence to Julian P. Casciano.

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Casciano, J.P., Singer, D.E., Kwong, W.J. et al. Anticoagulation Therapy for Patients with Non-Valvular Atrial Fibrillation. Am J Cardiovasc Drugs 12, 313–323 (2012). https://doi.org/10.1007/BF03261840

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  • Atrial Fibrillation
  • Warfarin
  • Stroke Risk
  • Bleeding Risk
  • CHADS2 Score