维生素 K 拮抗剂与利伐沙班在血液透析伴房颤患者中的安全性和疗效：一项多中心随机对照试验。

Safety and Efficacy of Vitamin K Antagonists versus Rivaroxaban in Hemodialysis Patients with Atrial Fibrillation: A Multicenter Randomized Controlled Trial.

机构信息

Division of Nephrology and Infectious Diseases, AZ Sint-Jan Brugge, Bruges, Belgium.

Department of Internal Medicine, Ghent University, Ghent, Belgium.

出版信息

J Am Soc Nephrol. 2021 Jun 1;32(6):1474-1483. doi: 10.1681/ASN.2020111566. Epub 2021 Mar 22.

DOI:10.1681/ASN.2020111566

PMID:33753537

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8259651/

Abstract

BACKGROUND

In patients with normal renal function or early stage CKD, the risk-benefit profile of direct oral anticoagulants (DOACs) is superior to that of vitamin K antagonists (VKAs). In patients on hemodialysis, the comparative efficacy and safety of DOACs versus VKAs are unknown.

METHODS

In the Valkyrie study, 132 patients on hemodialysis with atrial fibrillation were randomized to a VKA with a target INR of 2-3, 10 mg rivaroxaban daily, or rivaroxaban and vitamin K2 for 18 months. Patients continued the originally assigned treatment and follow-up was extended for at least an additional 18 months. The primary efficacy end point was a composite of fatal and nonfatal cardiovascular events. Secondary efficacy end points were individual components of the composite outcome and all-cause death. Safety end points were life-threatening, major, and minor bleeding.

RESULTS

Median (IQR) follow-up was 1.88 (1.01-3.38) years. Premature, permanent discontinuation of anticoagulation occurred in 25% of patients. The primary end point occurred at a rate of 63.8 per 100 person-years in the VKA group, 26.2 per 100 person-years in the rivaroxaban group, and 21.4 per 100 person-years in the rivaroxaban and vitamin K2 group. The estimated competing risk-adjusted hazard ratio for the primary end point was 0.41 (95% CI, 0.25 to 0.68; =0.0006) in the rivaroxaban group and 0.34 (95% CI, 0.19 to 0.61; =0.0003) in the rivaroxaban and vitamin K2 group, compared with the VKA group. Death from any cause, cardiac death, and risk of stroke were not different between the treatment arms, but symptomatic limb ischemia occurred significantly less frequently with rivaroxaban than with VKA. After adjustment for competing risk of death, the hazard ratio for life-threatening and major bleeding compared with the VKA group was 0.39 (95% CI, 0.17 to 0.90; =0.03) in the rivaroxaban group, 0.48 (95% CI, 0.22 to 1.08; =0.08) in the rivaroxaban and vitamin K2 group and 0.44 (95% CI, 0.23 to 0.85; =0.02) in the pooled rivaroxaban groups.

CONCLUSIONS

In patients on hemodialysis with atrial fibrillation, a reduced dose of rivaroxaban significantly decreased the composite outcome of fatal and nonfatal cardiovascular events and major bleeding complications compared with VKA.

CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER

Oral Anticoagulation in Hemodialysis, NCT03799822.

摘要

背景

在肾功能正常或慢性肾脏病（CKD）早期的患者中，直接口服抗凝剂（DOAC）的风险效益比优于维生素 K 拮抗剂（VKA）。在接受血液透析的患者中，DOAC 与 VKA 的疗效和安全性比较尚不清楚。

方法

在 Valkyrie 研究中，132 例接受血液透析的房颤患者被随机分配至 VKA 组（目标 INR 为 2-3）、10mg 利伐沙班每日 1 次组或利伐沙班和维生素 K2 组，持续 18 个月。患者继续接受最初分配的治疗，随访时间至少延长 18 个月。主要疗效终点是致命和非致命心血管事件的复合终点。次要疗效终点是复合结局的各个组成部分和全因死亡。安全性终点是危及生命、主要和次要出血。

结果

中位（IQR）随访时间为 1.88（1.01-3.38）年。25%的患者过早、永久停止抗凝治疗。VKA 组、利伐沙班组和利伐沙班加维生素 K2 组的主要终点发生率分别为 63.8/100 人年、26.2/100 人年和 21.4/100 人年。竞争风险调整后的主要终点风险比为利伐沙班组 0.41（95%CI，0.25 至 0.68；=0.0006），利伐沙班加维生素 K2 组 0.34（95%CI，0.19 至 0.61；=0.0003），与 VKA 组相比。各组之间全因死亡、心源性死亡和卒中风险无差异，但利伐沙班组症状性肢体缺血发生率明显低于 VKA 组。在调整死亡竞争风险后，与 VKA 组相比，利伐沙班组的严重和主要出血的风险比为 0.39（95%CI，0.17 至 0.90；=0.03），利伐沙班加维生素 K2 组为 0.48（95%CI，0.22 至 1.08；=0.08），联合利伐沙班组为 0.44（95%CI，0.23 至 0.85；=0.02）。