FIX-凝血酶原时间监测可改善心房颤动患者华法林抗凝效果：一项比较FIX-华法林或直接口服抗凝剂与标准PT-华法林的随机试验的系统评价

Fiix-prothrombin time monitoring improves warfarin anticoagulation outcome in atrial fibrillation: a systematic review of randomized trials comparing Fiix-warfarin or direct oral anticoagulants to standard PT-warfarin.

作者信息

Onundarson P T, Arnar D O, Lund S H, Gudmundsdottir B R, Francis C W, Indridason O S

机构信息

Landspitali National University Hospital of Iceland, Reykjavik, Iceland.

University of Iceland Faculty of Medicine, Reykjavik, Iceland.

出版信息

Int J Lab Hematol. 2016 May;38 Suppl 1:78-90. doi: 10.1111/ijlh.12537.

DOI:10.1111/ijlh.12537

PMID:27426862

Abstract

BACKGROUND

Monitoring warfarin with Fiix-prothrombin time (Fiix-PT), which is only affected by coagulation factors II and X, stabilizes anticoagulation and reduces thromboembolism compared to PT/INR monitoring. We compared outcome in nonvalvular atrial fibrillation (NVAF) patients treated with Fiix-warfarin, direct oral anticoagulants (DOACs), or PT-warfarin.

METHODS

A systematic efficacy and safety assessment by retrieving data from the Fiix trial and the four major phase III DOAC trials in NVAF. Prespecified outcomes included stroke and systemic embolism (SSE), SSE and myocardial infarction (MI), major bleeding (MB), composite major vascular events (SSEMI and MB; CMVE), and deaths. We calculated relative risk, 95% CI, and 95% confidence limits (CL) for each outcome and performed meta-analysis using fixed- and random-effects modeling.

RESULTS

There were 613 and 628 observation years with Fiix-warfarin and PT-warfarin in the Fiix trial, and 70 628 and 57 962 with DOACs and PT-warfarin in DOAC trials. Populations were comparable although death rates were lower in the Fiix trial. Compared to pooled PT-warfarin, Fiix-warfarin reduced SSE (RR 0.54;95% CI 0.26-1.10/95% CL <1.00), SSEMI (0.51;0.26-0.99/<0.90), MB (RR 0.63;0.37-1.07/<0.99), and CMVE (RR 0.66;0.43-1.00/<0.94). Vascular death was lower (RR 0.13;0.04-0.47/<0.42). Compared to pooled DOACs, Fiix-warfarin consistently had lower point estimates for the RR for efficacy and safety, but only significant for lower death rates (vascular death RR 0.14;0.04-0.49/<0.43). Meta-analysis comparing Fiix-warfarin and DOACs with PT-warfarin consistently found Fiix-warfarin to have the lowest point estimates for efficacy.

CONCLUSION

Monitoring warfarin with Fiix-PT reduces risk of vascular events in NVAF patients as much as DOACs. Warfarin monitored with Fiix-PT is an improved anticoagulant.

摘要

背景

使用仅受凝血因子II和X影响的Fiix-凝血酶原时间（Fiix-PT）监测华法林，与PT/INR监测相比，可稳定抗凝并减少血栓栓塞。我们比较了接受Fiix-华法林、直接口服抗凝剂（DOACs）或PT-华法林治疗的非瓣膜性心房颤动（NVAF）患者的结局。

方法

通过检索Fiix试验和NVAF的四项主要III期DOAC试验的数据进行系统的疗效和安全性评估。预先设定的结局包括卒中和全身性栓塞（SSE）、SSE和心肌梗死（MI）、大出血（MB）、复合重大血管事件（SSEMI和MB；CMVE）以及死亡。我们计算了每个结局的相对风险、95%置信区间（CI）和95%置信限（CL），并使用固定效应和随机效应模型进行荟萃分析。

结果

在Fiix试验中，Fiix-华法林和PT-华法林分别有613和628个观察年，在DOAC试验中，DOACs和PT-华法林分别有70628和57962个观察年。尽管Fiix试验中的死亡率较低，但人群具有可比性。与汇总的PT-华法林相比，Fiix-华法林降低了SSE（RR 0.54；95% CI 0.26 - 1.10/95% CL <1.00）、SSEMI（0.51；0.26 - 0.99/<0.90）、MB（RR 0.63；0.37 - 1.07/<0.99）和CMVE（RR 0.66；0.43 - 1.00/<0.94）。血管性死亡较低（RR 0.13；0.04 - 0.47/<0.42）。与汇总的DOACs相比，Fiix-华法林在疗效和安全性的RR点估计值始终较低，但仅在较低死亡率方面具有显著性（血管性死亡RR 0.14；0.04 - 0.49/<0.43）。比较Fiix-华法林和DOACs与PT-华法林的荟萃分析始终发现Fiix-华法林在疗效方面的点估计值最低。