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Should We Test for CYP2C9 Before Initiating Anticoagulant Therapy in Patients with Atrial Fibrillation?

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Abstract

Background

Genetic variants of the warfarin sensitivity gene CYP2C9 have been associated with increased bleeding risk during warfarin initiation. Studies also suggest that such patients remain at risk throughout treatment.

Objective

Would testing patients with non-valvular atrial fibrillation (AF) for CYP2C9 before initiating warfarin improve outcomes?

Design

Markov state transition decision model.

Setting

Ambulatory or inpatient settings necessitating new initiation of anticoagulation.

Patients

The base case was a 69-year-old man with newly diagnosed non-valvular AF. Interventions included: (1) warfarin, (2) aspirin, or (3) no antithrombotic therapy without genetic testing; and genetic testing followed by (4) aspirin or (5) no antithrombotic therapy in those with culprit CYP2C9 alleles.

Measures

Quality-adjusted life years (QALYs).

Results

In the base case, testing and treating patients with CYP2C9*2 and/or CYP2C9*3 with aspirin rather than warfarin was best (8.97 QALYs). However, warfarin without genetic testing was a close second (8.96 QALYs), a difference of roughly 5 days. Sensitivity analyses demonstrated that genetic testing followed by aspirin was best for patients at lower risk of embolic events. Warfarin without testing was preferred if the rate of embolic events was greater than 5% per year, or the risk of major bleeding while receiving warfarin was lower.

Conclusion

For patients at average risk for ischemic stroke due to AF and at average risk for major hemorrhage, treatment based on genetic testing offers no benefit compared to warfarin initiation without testing. The gain from testing may be larger in patients at lower risk of embolic events or at greater risk of bleeding.

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Acknowledgements

Mark H. Eckman: National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK075599), National Heart, Lung, and Blood Institute (K30 HL078581-01), and Foundation for Informed Medical Decision Making.

Steven M. Greenberg: National Institutes of Neurological Disorders and Stroke (R01 NS059727).

Jonathan Rosand: National Institutes of Neurological Disorders and Stroke (R01 NS059727), and the Deane Institute for Integrative Study of Atrial Fibrillation and Stroke.

We are grateful to Dr. Brian F. Gage in the Division of General Medical Sciences, Washington University in St. Louis for his help and generous contributions.

Conflict of Interest

None disclosed.

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Authors and Affiliations

  1. Division of General Internal Medicine and the Center for Clinical Effectiveness, University of Cincinnati Medical Center, University of Cincinnati (MHE), P.O. Box 670535, Cincinnati, OH, 45267-0535, USA

    Mark H. Eckman MD, MS

  2. Research Group, Department of Neurology (SMG, JR) and Center for Human Genetic Research (JR), Massachusetts General Hospital, Boston, MA, USA

    Steven M. Greenberg MD, PhD & Jonathan Rosand MD, MSc

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  1. Mark H. Eckman MD, MS
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Correspondence to Mark H. Eckman MD, MS.

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Eckman, M.H., Greenberg, S.M. & Rosand, J. Should We Test for CYP2C9 Before Initiating Anticoagulant Therapy in Patients with Atrial Fibrillation?. J GEN INTERN MED 24, 543–549 (2009). https://doi.org/10.1007/s11606-009-0927-7

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