直接口服抗凝剂与维生素K拮抗剂对抗抗磷脂综合征：系统回顾和荟萃分析

IF 4.6 2区医学 Q1 RHEUMATOLOGY

Seminars in arthritis and rheumatism Pub Date : 2025-05-01 DOI:10.1016/j.semarthrit.2025.152741

Alessandra Ida Celia , Giovanni Maria Vescovo , Gianmarco Sarto , Cristiano Alessandri , Antonio Iaconelli , Domenico D’Amario , Giacomo Frati , Fabrizio Conti , Sebastiano Sciarretta , Dominick J Angiolillo , Andrea Fava , Michelle A Petri , Behnood Bikdeli , Mattia Galli

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引用次数: 0

摘要

背景：比较直接口服抗凝剂（DOACs）与维生素K拮抗剂（VKAs）对血栓性抗磷脂综合征（APS）患者的疗效和安全性的随机对照试验（rct）得出了不一致的结果，部分原因是在罕见疾病人群中进行rct的固有挑战。我们进行了系统回顾和荟萃分析，以评估DOACs与vka在血栓性APS中的比较效果。方法纳入血栓性APS患者DOACs与vka的随机对照试验和观察性研究。主要终点是动脉血栓形成事件（ATE）和静脉血栓形成事件（VTE）的综合。发病率比（IRRs）和相关的95%置信区间（CI）用于解释不同的随访时间。GRADE用于评价证据的确定性。12项研究，4项随机研究和8项观察性研究，共纳入1307例APS患者。DOACs的使用与主要终点的增加相关(IRR 2.33；95% ci 1.18-4.58；GRADE=中度)，由ATE升高驱动(IRR 2.70；95% ci 1.42-5.13；GRADE=低)，与使用VKA相比。Vte (irr 0.98；95% ci 0.59-1.64；GRADE=low), major (IRR 0.83；95% ci 0.48-1.43；GRADE=低)和非主要(IRR 1.32；95% ci 0.81-2.14；GRADE=非常低)出血在两组间无显著差异。与vka相比，DOACs与心肌梗死的增加相关(IRR 4.71；95% ci 1.00-22.21；GRADE=非常低)和中风(IRR 7.48；95% ci 1.27-44.13；级=很低)。在一项专门的随机对照试验分析中一致观察到DOACs动脉血栓形成事件的风险增加，并通过同时使用单一抗血小板治疗来减轻风险。在血栓性APS患者中，与vka相比，DOACs的使用与血栓事件增加相关，主要由动脉血栓事件驱动。单一抗血小板治疗联合DOACs可能是vka的一个有希望的替代方案，值得进一步的专门研究。主要资金来源本研究未获资助。协议注册本研究在PROSPERO注册（CRD42024582033）。

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Direct oral anticoagulants versus Vitamin K antagonists in antiphospholipid syndrome: A systematic review and meta-analysis

Background

Randomized controlled trials (RCTs) comparing the efficacy and safety of direct oral anticoagulants (DOACs) versus Vitamin K antagonists (VKAs) in patients with thrombotic antiphospholipid syndrome (APS) have yielded inconsistent results, partly due to the inherent challenges of conducting RCTs in populations with rare medical conditions. We conducted a systematic review and meta-analysis to evaluate the comparative effects of DOACs versus VKAs in thrombotic APS.

Methods

RCTs and observational studies comparing DOACs versus VKAs in patients with thrombotic APS were included. The primary endpoint was a composite of arterial (ATE) and venous thrombotic events (VTE). Incidence rate ratios (IRRs) and associated 95 % confidence intervals (CI) were used to account for different follow-up durations. GRADE was used for rating the certainty of evidence.

Findings

Twelve studies, four randomized and eight observational, encompassing a total of 1307 APS patients were included. The use of DOACs was associated with an increase in the primary endpoint (IRR 2.33; 95 % CI 1.18–4.58; GRADE=moderate) driven by increased ATE (IRR 2.70; 95 % CI 1.42–5.13; GRADE=low), compared with the use of VKA. VTE (IRR 0.98; 95 % CI 0.59–1.64; GRADE=low), major (IRR 0.83; 95 % CI 0.48–1.43; GRADE=low) and non-major (IRR 1.32; 95 % CI 0.81–2.14; GRADE=very low) bleeding did not differ significantly between groups. Compared with VKAs, DOACs were associated with an increase in myocardial infarction (IRR 4.71; 95 % CI 1.00–22.21; GRADE=very low) and stroke (IRR 7.48; 95 % CI 1.27–44.13; GRADE=very low). The increased risk of arterial thrombotic events with DOACs was consistently observed in a dedicated analysis of RCTs and was mitigated by the concomitant use of single antiplatelet therapy.

Interpretation

In patients with thrombotic APS, the use of DOACs is associated with increased thrombotic events compared with VKAs, mainly driven by arterial thrombotic events. A single antiplatelet therapy combined with DOACs maight offer a promising alternative to VKAs, warranting further dedicated investigations.

Primary Funding Source

The study was not funded.

Protocol registration

This study is registered in PROSPERO (CRD42024582033).

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来源期刊

Seminars in arthritis and rheumatism 医学-风湿病学

CiteScore

9.20

自引率

4.00%

发文量

176

审稿时长

46 days

期刊介绍： Seminars in Arthritis and Rheumatism provides access to the highest-quality clinical, therapeutic and translational research about arthritis, rheumatology and musculoskeletal disorders that affect the joints and connective tissue. Each bimonthly issue includes articles giving you the latest diagnostic criteria, consensus statements, systematic reviews and meta-analyses as well as clinical and translational research studies. Read this journal for the latest groundbreaking research and to gain insights from scientists and clinicians on the management and treatment of musculoskeletal and autoimmune rheumatologic diseases. The journal is of interest to rheumatologists, orthopedic surgeons, internal medicine physicians, immunologists and specialists in bone and mineral metabolism.