Clinical Pharmacy and Practice Section, College of Pharmacy, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar.
College of Pharmacy, QU Health, Qatar University, Doha, Qatar.
J Thromb Thrombolysis. 2020 May;49(4):659-666. doi: 10.1007/s11239-020-02102-x.
There is no strong evidence on pharmacogenetics role on the quality of INR control after the initiation phase and on the maintenance of stable INR on the long term as measured by the time in therapeutic range (TTR). The benefit of a score such as SAMe-TTR is that it can preemptively guide clinicians on whether to start the patient on warfarin or direct oral anticoagulant. To determine the association between genetic variants in CYP2C9, VKORC1, and CYP4F2 and TTR. To validate SAMe-TTR score predictive ability on the quality of anticoagulation in Qatari patients. This is an observational nested case-control study that was conducted on a cohort of Qatari patients treated with warfarin with previously identified genotype for the CYP2C9, VKORC1, and CYP2F4. The sample size of this cohort was 148 patients. Mean TTR was 62.7 ± 21%. TTR was not significantly different among carriers of the CYP2C9*2 &3, VKORC1(-1639G>A) or CYP4F23 compared to their non-carriers alleles. None of the factors in the SAMe-TTR score had a significant effect on the TTR except for the female gender where TTR was significantly lower in females (n = 89) compared to males (n = 59) (59.6 ± 21% vs. 67.2 ± 20%, p = 0.03). Furthermore, patients with SAMe-TTR score of zero had significantly better TTR compared to those with higher scores (76.5 ± 17% vs. 61.8 ± 21%, p = 0.04). Logistic regression analysis showed that high SAMe-TTR score was the only statistically significant predicting factor of poor INR control (odds ratio (OR) 5.7, 95% confidence interval (CI) 1.1-28.3, p = 0.034). Genetic variants have no contribution to the quality of INR control. SAMe-TTR score was predictive for the poor quality of anticoagulation in a cohort of Qatari patients.
在启动阶段后，遗传药理学对 INR 控制质量的作用以及通过治疗范围时间 (TTR) 衡量的 INR 长期稳定性方面没有强有力的证据。SAMe-TTR 等评分的好处是，它可以预先指导临床医生是否开始给患者使用华法林或直接口服抗凝剂。确定 CYP2C9、VKORC1 和 CYP4F2 基因变异与 TTR 之间的关联。验证 SAMe-TTR 评分对卡塔尔患者抗凝质量的预测能力。这是一项观察性巢式病例对照研究，在接受华法林治疗的卡塔尔患者队列中进行，该队列先前已确定 CYP2C9、VKORC1 和 CYP2F4 的基因型。该队列的样本量为 148 例患者。平均 TTR 为 62.7±21%。CYP2C92 和3、VKORC1(-1639G>A)或 CYP4F2*3 携带者的 TTR 与非携带者的 TTR 相比没有显著差异。SAMe-TTR 评分中的除女性性别以外的其他因素对 TTR 均无显著影响，而女性 TTR 明显低于男性（n=89）比男性（n=59）（59.6±21%比 67.2±20%，p=0.03）。此外，SAMe-TTR 得分为零的患者的 TTR 明显好于得分较高的患者（76.5±17%比 61.8±21%，p=0.04）。Logistic 回归分析显示，高 SAMe-TTR 评分是 INR 控制不佳的唯一具有统计学意义的预测因素（比值比 (OR) 5.7，95%置信区间 (CI) 1.1-28.3，p=0.034）。遗传变异对 INR 控制质量没有贡献。SAMe-TTR 评分可预测卡塔尔患者群体抗凝质量差。
