1. A Pharmacogenetic versus a Clinical Algorithm for Warfarin Dosing
- Author
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Kimmel, Stephen E, French, Benjamin, Kasner, Scott E, Johnson, Julie A, Anderson, Jeffrey L, Gage, Brian F, Rosenberg, Yves D, Eby, Charles S, Madigan, Rosemary A, McBane, Robert B, Abdel-Rahman, Sherif Z, Stevens, Scott M, Yale, Steven, Mohler, Emile R, Fang, Margaret C, Shah, Vinay, Horenstein, Richard B, Limdi, Nita A, Muldowney, James AS, Gujral, Jaspal, Delafontaine, Patrice, Desnick, Robert J, Ortel, Thomas L, Billett, Henny H, Pendleton, Robert C, Geller, Nancy L, Halperin, Jonathan L, Goldhaber, Samuel Z, Caldwell, Michael D, Califf, Robert M, and Ellenberg, Jonas H
- Subjects
Hematology ,Genetics ,Clinical Research ,Clinical Trials and Supportive Activities ,Evaluation of treatments and therapeutic interventions ,Development of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,5.1 Pharmaceuticals ,Adult ,Aged ,Algorithms ,Anticoagulants ,Aryl Hydrocarbon Hydroxylases ,Cytochrome P-450 CYP2C9 ,Double-Blind Method ,Female ,Follow-Up Studies ,Genotype ,Hemorrhage ,Humans ,International Normalized Ratio ,Male ,Pharmacogenetics ,Thromboembolism ,Treatment Failure ,Vitamin K Epoxide Reductases ,Warfarin ,COAG Investigators ,Medical and Health Sciences ,General & Internal Medicine - Abstract
BackgroundThe clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results.MethodsWe randomly assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm that included both clinical variables and genotype data or to one that included clinical variables only. All patients and clinicians were unaware of the dose of warfarin during the first 4 weeks of therapy. The primary outcome was the percentage of time that the international normalized ratio (INR) was in the therapeutic range from day 4 or 5 through day 28 of therapy.ResultsAt 4 weeks, the mean percentage of time in the therapeutic range was 45.2% in the genotype-guided group and 45.4% in the clinically guided group (adjusted mean difference, [genotype-guided group minus clinically guided group], -0.2; 95% confidence interval, -3.4 to 3.1; P=0.91). There also was no significant between-group difference among patients with a predicted dose difference between the two algorithms of 1 mg per day or more. There was, however, a significant interaction between dosing strategy and race (P=0.003). Among black patients, the mean percentage of time in the therapeutic range was less in the genotype-guided group than in the clinically guided group. The rates of the combined outcome of any INR of 4 or more, major bleeding, or thromboembolism did not differ significantly according to dosing strategy.ConclusionsGenotype-guided dosing of warfarin did not improve anticoagulation control during the first 4 weeks of therapy. (Funded by the National Heart, Lung, and Blood Institute and others; COAG ClinicalTrials.gov number, NCT00839657.).
- Published
- 2013