Genetic and Non-Genetic Factors Affecting the Quality of Anticoagulation Control and Vascular Events in Atrial Fibrillation.

Warfarin has a narrow therapeutic window. We hypothesized that genetic factors related to warfarin metabolism (CYP2C9) and activity (VKORC1) would show stronger associations than modifiable factors with the quality of anticoagulation control and risks for thromboembolism and hemorrhage. In this retrospective cohort analysis, clinical and genetic data were collected from 380 patients with atrial fibrillation (AF) who were followed for an average observation period of 4 years. We evaluated the factors associated with time in therapeutic range (TTR, international normalized ratio [INR]: 2-3) and vascular events (either thromboembolic or hemorrhagic), including both genetic (CYP2C9 and VKORC1 genotype) and modifiable factors (anticoagulation service and warfarin dose assessment interval). The genotypic frequency of CYP2C9*3 (rs1057910) was 9.5% and that of VKORC1 1173C>T (rs9934438) was 16.3%. TTR showed dependence on VKORC1 polymorphism: TTR was higher in carriers of the VKORC1 1173C>T than of the VKORC1 TT genotype (61.7 ± 16.0% versus 56.7 ± 17.4%, P = .031). Multivariate testing showed that the VKORC1 genotype and anticoagulation service were independently related to labile INRs (TTR <65%). Vascular events were observed in 66 patients (18.4%) during the study period. A Cox proportional hazard model showed that the use of anticoagulation service and patients' characteristics, such as AF-thromboembolic risk (CHA2DS2-VASc score: Congestive heart failure, Hypertension, Age 75 years or older, Diabetes mellitus, previous Stroke or transient ischemic attack, Vascular disease, Age 65 to 74 years, female) and consequence (neurologic disability), but not genetic factors, were independently associated with vascular events. Both genetic factor (VKORC1 genotype) and clinical efforts (anticoagulation service) influenced the quality of anticoagulation control. However, clinical events were more strongly associated with patient characteristics and clinical efforts than with genetic factors.

Park YK ，Lee MJ ，Kim JH ，Lee JS ，Park RW ，Kim GM ，Chung CS ，Lee KH ，Kim JS ，Lee SY ，Bang OY ... -  《-》

Warfarin dose requirements with different genotypes of CYP2C9 and VKORC1 for patients with atrial fibrillation and valve replacement.

Chen W ，Wu L ，Liu X ，Shen Y ，Liang Y ，Zhu J ，Tan H ，Yang Y ，Liu Q ，Wang M ，Liu L ，Wang X ... -  《INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS》

Effect of gene polymorphims on the warfarin treatment at initial stage.

Liu J ，Jiang HH ，Wu DK ，Zhou YX ，Ye HM ，Li X ，Luo ZY ，Guo Z ，Zhang YL ，Wang YC ，Zhang W ，Zhou HH ，Wang LS ... -  《-》

A new algorithm to predict warfarin dose from polymorphisms of CYP4F2 , CYP2C9 and VKORC1 and clinical variables: derivation in Han Chinese patients with non valvular atrial fibrillation.

Wei M ，Ye F ，Xie D ，Zhu Y ，Zhu J ，Tao Y ，Yu F ... -  《-》

Rationale, design, and preliminary results of the Quebec Warfarin Cohort Study.

Over- and undercoagulation with warfarin are associated with hemorrhagic and thromboembolic events, respectively. Genetic and clinical factors affect warfarin response, and the causes of this variability remain unclear. We present descriptive statistics and test for predictors of poor anticoagulation control. The Quebec Warfarin Cohort (QWC) comprises 1059 new warfarin users, with prospective follow-up using telephone questionnaires every 3 months for 1 year, and using healthcare administrative databases (RAMQ and Med-Echo) for 5 years prior to cohort entry and up to 10 years following active patient participation. Genetic material was collected, and genotyping of CYP2C9 and VKORC1 genes was conducted. Measured outcomes included the percentage of time patients spent within therapeutic range, anticoagulation control, warfarin dose, bleeding, and thromboembolic events. We report baseline characteristics and outcomes after 1 year of follow-up. Poor anticoagulation control was defined as time in therapeutic range <60% in the 3- to 12-month interval. Participants had a mean age of 71 years, and 62% were men. The most common indication for warfarin was atrial fibrillation (87%). Mean time in therapeutic range was 56% (±25%) in the 3 months following warfarin initiation, and 70% (±21%) in the 3- to 12-month interval. During follow-up, the rate of stroke or systemic embolism was 1.8 events per 100 person-years; for major bleeding events, 3.3 events per 100 person-years. Independent predictors of poor anticoagulation control were chronic kidney disease, heart failure, dyslipidemia, and age. The QWC represents a good research cohort to investigate clinical and genetic factors in a warfarin-anticoagulated population.

Perreault S ，Shahabi P ，Côté R ，Dumas S ，Rouleau-Mailloux É ，Feroz Zada Y ，Provost S ，Mongrain I ，Dorais M ，Huynh T ，Kouz S ，Diaz A ，Blostein M ，de Denus S ，Turgeon J ，Ginsberg J ，Lelorier J ，Lalonde L ，Busque L ，Kassis J ，Talajic M ，Tardif JC ，Dubé MP ... -  《-》