利伐沙班与华法林在高危非瓣膜型房颤合并 重度颅内动脉狭窄脑梗死患者中的 应用效果比较

Comparison of Application Efficacy of Rivaroxaban and Warfarin in Patients with High-Risk Non-Valvular Atrial Fibrillation Complicated by Severe Intracranial Artery Stenosis and Cerebral Infarction

摘要: 目的：探讨利伐沙班与华法林在高危非瓣膜型房颤(non-valvular atrial fibrillation, NVAF)合并症状性重度颅内动脉粥样硬化性狭窄(intracranial atherosclerotic stenosis, ICAS)脑梗死患者中的治疗效果及安全性差异。方法：选取2021年1月至2023年12月在我院神经内科住院治疗的高危NVAF合并重度ICAS脑梗死患者100例，根据抗凝方案不同分为利伐沙班组(n = 50)和华法林组(n = 50)。两组患者均接受规范化卒中二级预防治疗，在此基础上分别给予利伐沙班或华法林抗凝治疗。比较两组患者抗凝治疗前及治疗后1个月的凝血功能指标[纤维蛋白原(FIB)、凝血酶时间(TT)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)]、心肌缺血相关标志物[肌钙蛋白I (cTnI)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)]、血液流变学指标[全血高切黏度、低切黏度、血浆黏度、红细胞聚集指数(EAI)]及血管内皮功能指标[血管性血友病因子(vWF)、血管紧张素II (Ang II)、内皮素1 (ET-1)、血管内皮生长因子(VEGF)]的变化，并随访至少12个月，记录出血事件及栓塞事件发生情况。同时，详细评估华法林组的抗凝治疗质量，包括治疗窗内时间(TTR)均值、TTR分布及INR值稳定性。结果：治疗后，利伐沙班组FIB水平低于华法林组，TT、APTT适度延长(P < 0.05)；利伐沙班组cTnI、CK-MB及LDH水平均低于华法林组(P < 0.05)。同时，利伐沙班组全血高切黏度、低切黏度、血浆黏度及EAI均较华法林组降低(P < 0.05)，vWF、Ang II及ET-1水平低于华法林组，VEGF水平高于华法林组(P < 0.05)。华法林组平均TTR为(62.3 ± 11.5)%，其中TTR ≥ 65%的患者占42.0%，TTR < 50%的患者占24.0%；INR值波动范围为1.2~4.8，超出治疗窗的次数占总监测次数的37.7%。随访期间，利伐沙班组出血事件及复发缺血性脑卒中发生率低于华法林组(P < 0.05)。结论：在高危NVAF合并症状性重度ICAS脑梗死患者中，利伐沙班较华法林能够在有效抗凝的同时改善血液流变学状态和血管内皮功能，减轻心肌损伤相关指标水平，并在临床应用中表现出更好的安全性，为该类复杂患者的个体化抗凝治疗提供了可行选择。

Abstract: Objective: To explore the differences in therapeutic efficacy and safety between rivaroxaban and warfarin in patients with high-risk non-valvular atrial fibrillation (NVAF) complicated by symptomatic severe intracranial atherosclerotic stenosis (ICAS) and cerebral infarction. Methods: A total of 100 patients with high-risk NVAF combined with severe ICAS and cerebral infarction hospitalized in the Department of Neurology of our hospital from January 2021 to December 2023 were enrolled and divided into rivaroxaban group (n = 50) and warfarin group (n = 50) according to different anticoagulation regimens. Both groups received standardized secondary prevention of stroke, on the basis of which rivaroxaban or warfarin was administered for anticoagulant therapy, respectively. The changes of coagulation function indicators including fibrinogen (FIB), thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (APTT), myocardial ischemia-related markers including cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH), hemorheological parameters including whole blood high shear viscosity, low shear viscosity, plasma viscosity and erythrocyte aggregation index (EAI), as well as vascular endothelial function indicators including von Willebrand factor (vWF), angiotensin II (Ang II), endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) were compared between the two groups before anticoagulation and at 1 month after treatment. All patients were followed up for at least 12 months, and the incidence of bleeding events and thromboembolic events was recorded. Meanwhile, the quality of anticoagulation in the warfarin group was evaluated in detail, including the mean time in therapeutic range (TTR), TTR distribution and the stability of INR values. Results: After treatment, the level of FIB in the rivaroxaban group was lower than that in the warfarin group, while TT and APTT were moderately prolonged (P < 0.05). The levels of cTnI, CK-MB and LDH in the rivaroxaban group were significantly lower than those in the warfarin group (P < 0.05). Moreover, the whole blood high shear viscosity, low shear viscosity, plasma viscosity and EAI in the rivaroxaban group were all decreased compared with the warfarin group (P < 0.05). The levels of vWF, Ang II and ET-1 were lower, while VEGF level was higher in the rivaroxaban group (P < 0.05). In the warfarin group, the average TTR was (62.3 ± 11.5)%, 42.0% of patients had TTR ≥ 65%, and 24.0% had TTR < 50%. The INR value fluctuated from 1.2 to 4.8, and the frequency of INR beyond the therapeutic window accounted for 37.7% of the total monitoring times. During the follow-up period, the incidence of bleeding events and recurrent ischemic stroke in the rivaroxaban group was lower than that in the warfarin group (P < 0.05). Conclusion: For patients with high-risk NVAF complicated by symptomatic severe ICAS and cerebral infarction, compared with warfarin, rivaroxaban can effectively exert anticoagulant effect, improve hemorheological status and vascular endothelial function, reduce the levels of myocardial injury-related indicators, and present better clinical safety. It provides a feasible option for individualized anticoagulation therapy in such complex patients.