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

source extracted confidence: high 2026-04-09
#humans #antiphospholipid-syndrome #anticoagulants #vitamin-k #administration-oral

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

Celia et al., 2025 | Semin Arthritis Rheum | Meta Analysis

Citation

Celia Alessandra Ida, Vescovo Giovanni Maria, ... Galli Mattia. Direct oral anticoagulants versus Vitamin K antagonists in antiphospholipid syndrome: A systematic review and meta-analysis. Semin Arthritis Rheum. 2025-Aug;73:152741. doi:10.1016/j.semarthrit.2025.152741

Abstract

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).

Key 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 d

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population thrombotic antiphospholipid syndrome
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • Humans
  • Antiphospholipid Syndrome
  • Anticoagulants
  • Vitamin K
  • Administration, Oral
  • Randomized Controlled Trials as Topic
  • Thrombosis

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Systematic Review, Meta-Analysis, Comparative Study
  • Vertical: vitamin-k

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09