Department of Clinical Laboratory, Wuhan Asia Heart Hospital, Wuhan University.
Laboratory of Molecular Cardiology, Wuhan Asia Heart Hospital, Wuhan University, Wuhan, China.
Ther Drug Monit. 2019 Dec;41(6):748-754. doi: 10.1097/FTD.0000000000000664.
Genotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry; yet, its utility in Chinese patients with heart valve replacement remains unresolved.
A total of 2264 patients who underwent heart valve replacement at Wuhan Asia Heart Hospital were enrolled in this study. Patients were randomly divided into 2 groups, namely, a genotype-guided and a traditional clinically guided warfarin dosing group. In the genotype-guided group (n = 1134), genotyping for CYP2C9 and VKORC1 (-1639 G→A) was performed using TaqMan genotyping assay. Warfarin doses were predicted with the International Warfarin Pharmacogenetics Consortium algorithm. Patients in the control group (n = 1130) were clinically guided. The primary outcome was to compare the incidence of adverse events (major bleeding and thrombotic) during a 90-day follow-up period between 2 groups. Secondary objectives were to describe effects of the pharmacogenetic intervention on the first therapeutic-target-achieving time, the stable maintenance dose, and the hospitalization days.
A total of 2245 patients were included in the analysis. Forty-nine events occurred during follow-up. Genotype-guided dosing strategy did not result in a reduction in major bleeding (0.26% versus 0.63%; hazard ratio, 0.44; 95% confidence interval, 0.13-1.53; P = 0.20) and thrombotic events (0.89% versus 1.61%; hazard ratio, 0.56; 95% confidence interval, 0.27-1.17; P = 0.12) compared with clinical dosing group. Compared with traditional dosing, patients in the genotype-guided group reached their therapeutic international normalized ratio in a shorter time (3.8 ± 2.0 versus 4.4 ± 2.0 days, P < 0.001). There was no difference in hospitalization days (P = 0.28).
Warfarin pharmacogenetic testing according to the International Warfarin Pharmacogenetics Consortium algorithm cannot improve anticoagulation outcomes in Chinese patients with heart valve replacement.
一些随机试验表明，基因型指导的华法林剂量调整可改善欧洲血统个体的抗凝治疗结果；然而，其在接受心脏瓣膜置换术的中国患者中的应用仍未得到解决。
本研究共纳入 2264 例在武汉亚洲心脏病医院接受心脏瓣膜置换术的患者。患者被随机分为 2 组，即基因型指导和传统临床指导的华法林剂量调整组。在基因型指导组（n=1134）中，使用 TaqMan 基因分型检测法检测 CYP2C9 和 VKORC1（-1639 G→A）的基因型。采用国际华法林药物基因组学联合会（International Warfarin Pharmacogenetics Consortium，IWPC）算法预测华法林剂量。对照组（n=1130）患者接受临床指导。主要结局是比较两组患者在 90 天随访期间不良事件（大出血和血栓形成）的发生率。次要目标是描述药物遗传学干预对首次达到治疗目标时间、稳定维持剂量和住院天数的影响。
共纳入 2245 例患者进行分析。随访期间共发生 49 例事件。与临床剂量组相比，基因型指导剂量策略并未降低大出血（0.26%比 0.63%；风险比，0.44；95%置信区间，0.13-1.53；P=0.20）和血栓形成事件（0.89%比 1.61%；风险比，0.56；95%置信区间，0.27-1.17；P=0.12）的发生率。与传统剂量组相比，基因型指导组的患者达到治疗国际标准化比值的时间更短（3.8±2.0 比 4.4±2.0 天，P＜0.001）。两组患者的住院天数无差异（P=0.28）。
根据国际华法林药物基因组学联合会算法进行华法林药物遗传学检测并不能改善接受心脏瓣膜置换术的中国患者的抗凝治疗结果。
