背景:在心房颤动(AFib)患者中,直接口服抗凝剂(DOAC)优于华法林。然而,它们在AFib和癌症患者中的安全性和有效性尚无定论。
方法:我们通过模拟一项目标试验进行了一项回顾性队列研究。有癌症记录的患者(乳腺癌,前列腺,或肺),从2012-2019年监测中,新诊断为AFib的患者在AFib诊断后3个月内开始使用DOAC或华法林,流行病学,包括最终结果(SEER)-Medicare数据库。我们比较了缺血性中风的风险,大出血,和次要结果(静脉血栓栓塞,颅内出血,消化道出血,和非关键部位出血)在开始DOAC和华法林的患者之间。使用逆概率治疗权重和逆概率审查权重来调整两组之间不平衡的患者和疾病特征以及随访损失。使用加权合并逻辑回归以95%置信区间(95%CIs)的风险比(HRs)估计治疗效果。
结果:DOAC和华法林起始剂的卒中和大出血发生率分别为9.97和9.91和7.74vs.每1000人年9.24例,分别。在调整后的意向治疗分析中,与开始使用华法林的患者相比,开始使用DOAC的患者在缺血性卒中(HR=0.87,95%CI0.52~1.44)和大出血(HR=1.14,95%CI0.77~1.68)的风险方面无统计学差异.在调整后的符合方案分析中,缺血性卒中风险(HR=1.81,95%CI0.75-4.36)和大出血风险较低无统计学差异,但与华法林引发剂相比,DOAC引发剂的95%CI较宽(HR=0.35,95%CI0.12-0.99).次要结局的益处有利于DOAC。亚组和敏感性分析的结果保持一致。
结论:在AFib和癌症患者的治疗中,DOAC是华法林的安全有效的替代品。
BACKGROUND: Direct oral anticoagulants (DOACs) are preferred over
warfarin in patients with atrial fibrillation (AFib). However, their safety and effectiveness in patients with AFib and cancer are inconclusive.
METHODS: We conducted a retrospective cohort
study by emulating a target
trial. Patients with a record of cancer (breast, prostate, or lung), newly diagnosed with AFib initiated DOACs or warfarin within 3 months after AFib diagnosis from the 2012-2019 Surveillance, Epidemiology, and End Results (SEER)-Medicare database were included. We compared the risk of ischemic stroke, major bleeding, and secondary outcomes (venous thromboembolism, intracranial bleeding, gastrointestinal bleeding, and non-critical site bleeding) between patients who initiated DOACs and
warfarin. Inverse probability treatment weights and inverse probability censoring weights were used to adjust imbalanced patient and disease characteristics and loss to follow-up between the two groups. Weighted pooled logistic regression were used to estimate treatment effect with hazard ratios (HRs) with 95% confidence interval (95% CIs).
RESULTS: The incidence rates of stroke and major bleeding between DOAC and
warfarin initiators were 9.97 vs. 9.91 and 7.74 vs. 9.24 cases per 1000 person-years, respectively. In adjusted intention-to-treat analysis, patients initiated DOACs had no statistically significant difference in risk of ischemic stroke (HR = 0.87, 95% CI 0.52-1.44) and major bleeding (HR = 1.14, 95% CI 0.77-1.68) compared to those initiated warfarin. In adjusted per-protocol analysis, there was no statistical difference in risk of ischemic stroke (HR = 1.81, 95% CI 0.75-4.36) and lower risk for major bleeding, but the 95% CI was wide (HR = 0.35, 95% CI 0.12-0.99) among DOAC initiators compared to warfarin initiators. The benefits in secondary outcomes were in favor of DOACs. The findings remained consistent across subgroups and sensitivity analyses.
CONCLUSIONS: DOACs are safe and effective alternatives to
warfarin in the management of patients with AFib and cancer.