美国布列根和妇女医院和哈佛医学院Katsiaryna Bykov团队研究了静脉血栓栓塞住院90天后延长抗凝治疗的患者口服抗凝剂类型与不良临床结局的相关性。2022年3月15日出版的《美国医学会杂志》发表了这项成果。

静脉血栓栓塞症（VTE）管理指南建议至少使用口服抗凝剂治疗90天。关于持续治疗超过90天的最佳药物的证据有限。

为了比较在最初90天的抗凝治疗后，阿哌沙班、利伐沙班或华法林的处方对复发性VTE、大出血和死亡住院治疗结局的影响，研究组进行了一项探索性回顾性队列研究，使用来自按服务收费医疗保险（2009-2017年）和两个商业健康保险（2004-2018年）数据库的数据，包括64642名因VTE住院且出院后开始口服抗凝剂的成人，均持续治疗超过90天。

暴露因素为VTE最初90天治疗后服用阿哌沙班、利伐沙班或华法林。主要结局包括因复发性VTE住院和因大出血住院。使用倾向评分加权校正分析。患者从最初90天治疗结束时开始随访，直到治疗停止、结局、死亡、出院或可用数据结束。加权Cox比例风险模型用于估计风险比（HRs）和95%CI。

该研究包括9167名服用阿哌沙班的患者（平均年龄71岁；5491名[59.9%]为女性），12468名服用利伐沙班的患者（平均年龄69岁；7067名[56.7%]为女性）和43007名服用华法林的患者（平均年龄70岁；25404名[59.1%]为女性）。复发性VTE的中位随访时间为109天，严重出血的中位随访时间为108天。

倾向评分加权后，阿哌沙班组复发性VTE住院的发生率明显低于华法林组（分别为9.8与13.5/1000人-年），但阿哌沙班组和利伐沙班组之间没有显著差异（分别为9.8与11.6/1000人-年），利伐沙班组和华法林组之间亦无显著差异。

阿哌沙班组的大出血住院率为44.4/1000人-年，利伐沙班组为50.0/1000人-年，华法林组为47.1/1000人-年，阿哌沙班组与华法林组的HRs为0.92，阿哌沙班组与利伐沙班组的HRs为0.86，利伐沙班组与华法林组的HRs为1.07。

研究结果表明，对于因静脉血栓栓塞住院后给予延长时间口服抗凝治疗的患者，超过90天的阿哌沙班处方与超过90天的华法林处方相比，与复发性静脉血栓栓塞的住院率略低显著相关，但大出血住院率无显著差异。

附：英文原文

Title: Association of Type of Oral Anticoagulant Dispensed With Adverse Clinical Outcomes in Patients Extending Anticoagulation Therapy Beyond 90 Days After Hospitalization for Venous Thromboembolism

Author: Ajinkya Pawar, Joshua J. Gagne, Chandrasekar Gopalakrishnan, Geetha Iyer, Helen Tesfaye, Gregory Brill, Kristyn Chin, Katsiaryna Bykov

Issue&Volume: 2022/03/15

Abstract:

Importance  Guidelines for managing venous thromboembolism (VTE) recommend at least 90 days of therapy with oral anticoagulants. Limited evidence exists about the optimal drug for continuing therapy beyond 90 days.

Objective  To compare having prescriptions dispensed for apixaban, rivaroxaban, or warfarin after an initial 90 days of anticoagulation therapy for the outcomes of hospitalization for recurrent VTE, major bleeding, and death.

Design, Setting, and Participants  This exploratory retrospective cohort study used data from fee-for-service Medicare (2009-2017) and from 2 commercial health insurance (2004-2018) databases and included 64642 adults who initiated oral anticoagulation following hospitalization discharge for VTE and continued treatment beyond 90 days.

Exposures  Apixaban, rivaroxaban, or warfarin prescribed after an initial 90-day treatment for VTE.

Main Outcomes and Measures  Primary outcomes included hospitalization for recurrent VTE and hospitalization for major bleeding. Analyses were adjusted using propensity score weighting. Patients were followed up from the end of the initial 90-day treatment episode until treatment cessation, outcome, death, disenrollment, or end of available data. Weighted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs.

Results  The study included 9167 patients prescribed apixaban (mean [SD] age, 71 [14] years; 5491 [59.9%] women), 12468 patients prescribed rivaroxaban (mean [SD] age, 69 [14] years; 7067 [56.7%] women), and 43007 patients prescribed warfarin (mean [SD] age, 70 [15] years; 25404 [59.1%] women). The median (IQR) follow-up was 109 (59-228) days for recurrent VTE and 108 (58-226) days for major bleeding outcome. After propensity score weighting, the incidence rate of hospitalization for recurrent VTE was significantly lower for apixaban compared with warfarin (9.8 vs 13.5 per 1000 person-years; HR, 0.69 [95% CI, 0.49-0.99]), but the incidence rates were not significantly different between apixaban and rivaroxaban (9.8 vs 11.6 per 1000 person-years; HR, 0.80 [95% CI, 0.53-1.19]) or rivaroxaban and warfarin (HR, 0.87 [95% CI, 0.65-1.16]). Rates of hospitalization for major bleeding were 44.4 per 1000 person-years for apixaban, 50.0 per 1000 person-years for rivaroxaban, and 47.1 per 1000 person-years for warfarin, yielding HRs of 0.92 (95% CI, 0.78-1.09) for apixaban vs warfarin, 0.86 (95% CI, 0.71-1.04) for apixaban vs rivaroxaban, and 1.07 (95% CI, 0.93-1.24) for rivaroxaban vs warfarin.

Conclusions and Relevance  In this exploratory analysis of patients prescribed extended-duration oral anticoagulation therapy after hospitalization for VTE, prescription dispenses for apixaban beyond 90 days, compared with warfarin beyond 90 days, were significantly associated with a modestly lower rate of hospitalization for recurrent VTE, but no significant difference in rate of hospitalization for major bleeding. There were no significant differences for comparisons of apixaban vs rivaroxaban or rivaroxaban vs warfarin.

DOI: 10.1001/jama.2022.1920

Source: https://jamanetwork.com/journals/jama/article-abstract/2789970