Quality of oral anticoagulation control in Chinese patients with non-valvular atrial fibrillation: a prospective controlled study.

OBJECTIVE: The sex, age, medical history, treatment, tobacco use, race risk (SAMe-TT2R2) Score; the sex, age, medical history, treatment, tobacco use, genotype combination (SAMe-TT2G2) Score; and the so-called modified SAMe-TT2R2 scores have been proposed to predict the anticoagulation quality for patients with non-valvular atrial fibrillation (NVAF). The data from a prospective controlled study is used to validate the SAMe-TT2R2 and SAMe-TT2G2 scores in Chinese NVAF patients treated with warfarin and to evaluate the association of factors with time in therapeutic range (TTR) to predict the quality of oral anticoagulation control. METHODS: A total of 379 patients with NVAF under warfarin treatment for a three-month follow-up were included in this prospective, multicenter study. The quality of oral anticoagulation control was evaluated by the TTR. The TTR was dichotomized for binary logistic regression analysis, using a cutoff point for classification as an inadequate (TTR < 65.0%) control. RESULTS: The 379 NVAF patients had a mean TTR of 58.35 ± 26.33% and median SAMe-TT2R2 and SAMe-TT2G2 scores of 3 and 2, respectively. The discrimination performances of the SAMe-TT2R2 and SAMe-TT2G2 scores for inadequate anticoagulation control (TTR < 65.0%) were poor (c-index < 0.60). The gene frequency of CYP2C9*3 was 3.2% and that of VKORC1-1639 G > A was 89.3%. Genetic variation of CYP2C9*3 and VKORC1-1639 G > A did not affect TTR after initial treatment. The condition TTR < 65.0% was associated with an age below 60 without genotype-guided warfarin dose initiation and concomitant torasemide. CONCLUSIONS: A warfarin-dosing algorithm used for initial treatment of patients older than 60 helps to achieve a better quality of oral anticoagulation control, whereas concomitant torasemide can produce a negative effect. These findings provide useful information for future investigations on the quality of oral anticoagulation control in Chinese anticoagulation clinical practice.

Genotype-Guided Dosing of Warfarin in Chinese Adults: A Multicenter Randomized Clinical Trial.

BACKGROUND: Warfarin is an effective treatment for thromboembolic disease but has a narrow therapeutic index; optimal anticoagulation dosage can differ tremendously among individuals. We aimed to evaluate whether genotype-guided warfarin dosing is superior to routine clinical dosing for the outcomes of interest in Chinese patients. METHODS: We conducted a multicenter, randomized, single-blind, parallel-controlled trial from September 2014 to April 2017 in 15 hospitals in China. Eligible patients were ≥18 years of age, with atrial fibrillation or deep vein thrombosis without previous treatment of warfarin or a bleeding disorder. Nine follow-up visits were performed during the 12-week study period. The primary outcome measure was the percentage of time in the therapeutic range of the international normalized ratio during the first 12 weeks after starting warfarin therapy. RESULTS: A total of 660 participants were enrolled and randomly assigned to a genotype-guided dosing group or a control group under standard dosing. The genotype-guided dosing group had a significantly higher percentage of time in the therapeutic range than the control group (58.8% versus 53.2% [95% CI of group difference, 1.1-10.2]; P=0.01). The genotype-guided dosing group also achieved the target international normalized ratio sooner than the control group. In subgroup analyses, warfarin normal sensitivity group had an even higher percentage of time in the therapeutic range during the first 12 weeks compared with the control group (60.8% versus 48.9% [95% CI, 1.1-24.4]). The incidence of adverse events was low in both groups. CONCLUSIONS: The outcomes of genotype-guided warfarin dosing were superior to those of clinical standard dosing. These findings raise the prospect of precision warfarin treatment in China. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02211326.