Patient-specific decision-making for warfarin therapy in nonvalvular atrial fibrillation: how will screening with genetics and imaging help?
OBJECTIVE
Intracerebral hemorrhage (ICH) accounts for a majority of long-term morbidity and mortality associated with bleeding while on warfarin. Both ICH and warfarin-related ICH appear to have a genetic component. Furthermore, advanced neuroimaging using MRI can now identify individuals at increased risk of ICH. We explore whether screening strategies that include genetic profiling and neuroimaging might improve the safety of chronic anticoagulation for atrial fibrillation by identifying individuals from whom warfarin should be withheld.


METHODS
We used a Markov state transition decision model. Effectiveness was measured in quality-adjusted life-years. Data sources included the English language literature using MEDLINE searches and bibliographies from selected articles along with empirical data from our institutions. The base case was a 69-year-old man with newly diagnosed nonvalvular atrial fibrillation.


RESULTS
For patients at average risk for thromboembolic events and known to possess a hypothetical genetic profile increasing risk for warfarin ICH, anticoagulation remains the preferred strategy until the relative hazard of ICH exceeds 23.8. Genetic profiling would be favored for patients at low risk of thromboembolism (1.5% per year) if the hypothetical gene variant(s) conferred a relative risk of ICH >4.1. Screening strategies in which patients underwent genotyping and MRI before anticoagulation did not improve aggregate patient outcomes unless the predictive power of MRI exceeded current best guess estimates and patients were at low to moderate risk of thromboembolism.


CONCLUSIONS
Currently identified genetic markers of bleeding risk do not confer a risk of ICH sufficiently high to warrant routine genetic testing for patients at average risk of thromboembolism. Even if patients undergo screening with MRI as well as genotyping, currently available data on the role of MRI on risk of ICH and warfarin ICH do not support use of these tests for withholding anticoagulation in patients with atrial fibrillation.
Division of General Internal Medicine and the Center for Clinical Effectiveness, University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0535, USA. mark.eckman@uc.edu
Mark H
MH
Eckman
Lawrence K S
LK
Wong
Yannie O Y
YO
Soo
Wynnie
W
Lam
Song Ran
SR
Yang
Steven M
SM
Greenberg
Jonathan
J
Rosand
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications*; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D003661:Decision Support Techniques; D005819:Genetic Markers; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D020766:Intracranial Embolism / Q000209:etiology / Q000517:prevention & control; D008279:Magnetic Resonance Imaging; D008297:Male; D008390:Markov Chains; D012306:Risk; D013923:Thromboembolism / Q000235:genetics; D019851:Thrombophilia / Q000453:epidemiology / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000925:Anticoagulants; D005819:Genetic Markers; D014859:Warfarin