Mark H Eckman1, Steven M Greenberg, Jonathan Rosand. 1. Division of General Internal Medicine and Center for Clinical Effectiveness, University of Cincinnati Medical Center, University of Cincinnati (MHE), PO Box 670535, Cincinnati, OH 45267-0535, USA. mark.eckman@uc.edu
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.
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.
Authors: Daniel Woo; Laura R Sauerbeck; Brett M Kissela; Jane C Khoury; Jerzy P Szaflarski; James Gebel; Rakesh Shukla; Arthur M Pancioli; Edward C Jauch; Anil G Menon; Ranjan Deka; Janice A Carrozzella; Charles J Moomaw; Robert N Fontaine; Joseph P Broderick Journal: Stroke Date: 2002-05 Impact factor: 7.914
Authors: Carl van Walraven; Robert G Hart; Daniel E Singer; Andreas Laupacis; Stuart Connolly; Palle Petersen; Peter J Koudstaal; Yuchiao Chang; Beppie Hellemons Journal: JAMA Date: 2002-11-20 Impact factor: 56.272
Authors: Mitchell K Higashi; David L Veenstra; L Midori Kondo; Ann K Wittkowsky; Sengkeo L Srinouanprachanh; Fred M Farin; Allan E Rettie Journal: JAMA Date: 2002-04-03 Impact factor: 56.272
Authors: Robert J Stanton; Mark H Eckman; Daniel Woo; Charles J Moomaw; Mary Haverbusch; Matthew L Flaherty; Dawn O Kleindorfer Journal: Stroke Date: 2020-01-31 Impact factor: 7.914
Authors: Carlos Martes-Martinez; Cristian Méndez-Sepúlveda; Joel Millán-Molina; Matthew French-Kim; Heriberto Marín-Centeno; Giselle C Rivera-Miranda; José J Hernández-Muñoz; Jorge Duconge-Soler Journal: P R Health Sci J Date: 2017-09 Impact factor: 0.705
Authors: Gary Tse; Mengqi Gong; Guangping Li; Sunny Hei Wong; William K K Wu; Wing Tak Wong; Leonardo Roever; Alex Pui Wai Lee; Gregory Y H Lip; Martin C S Wong; Tong Liu Journal: Br J Clin Pharmacol Date: 2018-06-21 Impact factor: 4.335