BACKGROUND: The level of anticoagulation in response to a fixed-dose regimen of warfarin is difficult to predict during the initiation of therapy. We prospectively compared the effect of genotype-guided dosing with that of standard dosing on anticoagulation control in patients starting warfarin therapy. METHODS: We conducted a multicenter, randomized, controlled trial involving patients with atrial fibrillation or venous thromboembolism. Genotyping for CYP2C9*2, CYP2C9*3, and VKORC1 (-1639G→A) was performed with the use of a point-of-care test. For patients assigned to the genotype-guided group, warfarin doses were prescribed according to pharmacogenetic-based algorithms for the first 5 days. Patients in the control (standard dosing) group received a 3-day loading-dose regimen. After the initiation period, the treatment of all patients was managed according to routine clinical practice. The primary outcome measure was the percentage of time in the therapeutic range of 2.0 to 3.0 for the international normalized ratio (INR) during the first 12 weeks after warfarin initiation. RESULTS: A total of 455 patients were recruited, with 227 randomly assigned to the genotype-guided group and 228 assigned to the control group. The mean percentage of time in the therapeutic range was 67.4% in the genotype-guided group as compared with 60.3% in the control group (adjusted difference, 7.0 percentage points; 95% confidence interval, 3.3 to 10.6; P<0.001). There were significantly fewer incidences of excessive anticoagulation (INR ≥4.0) in the genotype-guided group. The median time to reach a therapeutic INR was 21 days in the genotype-guided group as compared with 29 days in the control group (P<0.001). CONCLUSIONS: Pharmacogenetic-based dosing was associated with a higher percentage of time in the therapeutic INR range than was standard dosing during the initiation of warfarin therapy. (Funded by the European Commission Seventh Framework Programme and others; ClinicalTrials.gov number, NCT01119300.).
BACKGROUND: The level of anticoagulation in response to a fixed-dose regimen of warfarin is difficult to predict during the initiation of therapy. We prospectively compared the effect of genotype-guided dosing with that of standard dosing on anticoagulation control in patients starting warfarin therapy. METHODS: We conducted a multicenter, randomized, controlled trial involving patients with atrial fibrillation or venous thromboembolism. Genotyping for CYP2C9*2, CYP2C9*3, and VKORC1 (-1639G→A) was performed with the use of a point-of-care test. For patients assigned to the genotype-guided group, warfarin doses were prescribed according to pharmacogenetic-based algorithms for the first 5 days. Patients in the control (standard dosing) group received a 3-day loading-dose regimen. After the initiation period, the treatment of all patients was managed according to routine clinical practice. The primary outcome measure was the percentage of time in the therapeutic range of 2.0 to 3.0 for the international normalized ratio (INR) during the first 12 weeks after warfarin initiation. RESULTS: A total of 455 patients were recruited, with 227 randomly assigned to the genotype-guided group and 228 assigned to the control group. The mean percentage of time in the therapeutic range was 67.4% in the genotype-guided group as compared with 60.3% in the control group (adjusted difference, 7.0 percentage points; 95% confidence interval, 3.3 to 10.6; P<0.001). There were significantly fewer incidences of excessive anticoagulation (INR ≥4.0) in the genotype-guided group. The median time to reach a therapeutic INR was 21 days in the genotype-guided group as compared with 29 days in the control group (P<0.001). CONCLUSIONS: Pharmacogenetic-based dosing was associated with a higher percentage of time in the therapeutic INR range than was standard dosing during the initiation of warfarin therapy. (Funded by the European Commission Seventh Framework Programme and others; ClinicalTrials.gov number, NCT01119300.).
Authors: Guido J Falcone; Farid Radmanesh; H Bart Brouwers; Thomas W K Battey; William J Devan; Valerie Valant; Miriam R Raffeld; Lennox P Chitsike; Alison M Ayres; Kristin Schwab; Joshua N Goldstein; Anand Viswanathan; Steven M Greenberg; Magdy Selim; James F Meschia; Devin L Brown; Bradford B Worrall; Scott L Silliman; David L Tirschwell; Matthew L Flaherty; Sharyl R Martini; Ranjan Deka; Alessandro Biffi; Peter Kraft; Daniel Woo; Jonathan Rosand; Christopher D Anderson Journal: Neurology Date: 2014-08-22 Impact factor: 9.910
Authors: Elisa Danese; Sara Raimondi; Martina Montagnana; Angela Tagetti; Taimour Langaee; Paola Borgiani; Cinzia Ciccacci; Antonio J Carcas; Alberto M Borobia; Hoi Y Tong; Cristina Dávila-Fajardo; Mariana Rodrigues Botton; Stephane Bourgeois; Panos Deloukas; Michael D Caldwell; Jim K Burmester; Richard L Berg; Larisa H Cavallari; Katarzyna Drozda; Min Huang; Li-Zi Zhao; Han-Jing Cen; Rocio Gonzalez-Conejero; Vanessa Roldan; Yusuke Nakamura; Taisei Mushiroda; Inna Y Gong; Richard B Kim; Keita Hirai; Kunihiko Itoh; Carlos Isaza; Leonardo Beltrán; Enrique Jiménez-Varo; Marisa Cañadas-Garre; Alice Giontella; Marianne K Kringen; Kari Bente Foss Haug; Hye Sun Gwak; Kyung Eun Lee; Pietro Minuz; Ming Ta Michael Lee; Steven A Lubitz; Stuart Scott; Cristina Mazzaccara; Lucia Sacchetti; Ece Genç; Mahmut Özer; Anil Pathare; Rajagopal Krishnamoorthy; Andras Paldi; Virginie Siguret; Marie-Anne Loriot; Vijay Kumar Kutala; Guilherme Suarez-Kurtz; Jamila Perini; Josh C Denny; Andrea H Ramirez; Balraj Mittal; Saurabh Singh Rathore; Hersh Sagreiya; Russ Altman; Mohamed Hossam A Shahin; Sherief I Khalifa; Nita A Limdi; Charles Rivers; Aditi Shendre; Chrisly Dillon; Ivet M Suriapranata; Hong-Hao Zhou; Sheng-Lan Tan; Vacis Tatarunas; Vaiva Lesauskaite; Yumao Zhang; Anke H Maitland-van der Zee; Talitha I Verhoef; Anthonius de Boer; Monica Taljaard; Carlo Federico Zambon; Vittorio Pengo; Jieying Eunice Zhang; Munir Pirmohamed; Julie A Johnson; Cristiano Fava Journal: Clin Pharmacol Ther Date: 2019-02-17 Impact factor: 6.875