Department of Pharmacy, The Second Xiangya Hospital, Central South University, No.139, People's Middle Street, Furong District, Changsha City, 40013, Hunan Porv., China.
Institute of Clinical Pharmacy, Central South University, Changsha, China.
BMC Cardiovasc Disord. 2023 May 31;23(1):279. doi: 10.1186/s12872-023-03321-9.
The anticoagulation effect of warfarin is usually evaluated by percentage of time in therapeutic range (PTTR), which is negatively correlated with the risk of warfarin adverse reactions. This study aimed to explore the effects of genetic and nongenetic factors on anticoagulation efficacy of warfarin during different therapeutic range.
We conducted an observational retrospective study aiming at evaluating the impact of clinical and genetic factors on PTTR from initial to more than six months treatment. This analysis included patients with heart valve replace (HVR) surgery who underwent long-term or life-long time treatment with standard-dose warfarin for anticoagulation control in Second Xiangya Hospital. All patients were followed for at least 6 months. We genotyped single nucleotide polymorphisms in VKORC1 and CYP2C9 associated with altered warfarin dose requirements and tested their associations with PTTR.
A total of 629 patients with intact clinical data and available genotype data were enrolled in this study, and only 38.63% patients achieved good anticoagulation control (PTTR > 0.6). Clinical factors, including male gender, older age, overweight, AVR surgery and stroke history, were associated with higher PTTR. Patients with VKORC1 -1639AA genotype had significantly higher PTTR level compared with GA/GG genotype carriers only in the first month of treatment. Patients with CYP2C93 allele had higher PTTR compared with CYP2C911 carriers. Moreover, compared with VKORC1 -1639 AG/GG carriers, INR > 4 was more likely to be present in patients with AA genotype. The frequency of CYP2C91*3 in patients with INR > 4 was significantly higher than these without INR > 4.
We confirmed the relevant factors of warfarin anticoagulation control, including genetic factors (VKORC1 -1639G > A and CYP2C9*3 polymorphisms) and clinical factors (male gender, older age, overweight, AVR surgery and stroke history), which could be helpful to individualize warfarin dosage and improve warfarin anticoagulation control during different treatment period.
华法林的抗凝效果通常通过治疗范围内的时间百分比（PTTR）来评估，PTTR 与华法林不良反应的风险呈负相关。本研究旨在探讨遗传和非遗传因素对华法林在不同治疗范围内抗凝效果的影响。
我们进行了一项观察性回顾性研究，旨在评估从初始治疗到超过 6 个月治疗期间，临床和遗传因素对 PTTR 的影响。该分析包括在第二湘雅医院接受心脏瓣膜置换（HVR）手术并长期或终身接受标准剂量华法林治疗以控制抗凝的患者。所有患者的随访时间均至少为 6 个月。我们对与改变华法林剂量需求相关的 VKORC1 和 CYP2C9 的单核苷酸多态性进行基因分型，并测试其与 PTTR 的关联。
共有 629 名具有完整临床数据和可用基因型数据的患者纳入本研究，只有 38.63%的患者达到了良好的抗凝控制（PTTR＞0.6）。临床因素，包括男性、年龄较大、超重、AVR 手术和中风史，与较高的 PTTR 相关。与 GA/GG 基因型携带者相比，仅在治疗的第一个月，VKORC1-1639AA 基因型患者的 PTTR 水平显著升高。与 CYP2C911 携带者相比，CYP2C93 等位基因携带者的 PTTR 更高。此外，与 VKORC1-1639AG/GG 携带者相比，AA 基因型患者的 INR＞4 更有可能出现。INR＞4 的患者中 CYP2C91*3 的频率明显高于 INR＞4 的患者。
我们证实了华法林抗凝控制的相关因素，包括遗传因素（VKORC1-1639G＞A 和 CYP2C9*3 多态性）和临床因素（男性、年龄较大、超重、AVR 手术和中风史），这有助于对华法林剂量进行个体化，并改善不同治疗期间的华法林抗凝控制。
