Comparative effectiveness and outcomes of direct oral anticoagulants vs. vitamin K antagonists (VKA) in atrial arrhythmias patients with isolated lupus anticoagulant without antiphospholipid syndrome: A real-world cohort analysis

Authors

• Omar Obeidat, Department of Internal Medicine, Division of Geriatrics and Palliative Medicine, University of Texas Medical Branch at Galveston, Galveston, USA.
• Laith Alhuneafat, Department of Cardiovascular Medicine, University of Minnesota, Minneapolis, MN, USA.
• Mohamed F. Ismail, Advocate Health - MidwestFollow
• Stephanie Elbanna, Department of Internal Medicine, University of Texas Medical Branch at Galveston, Galveston, USA.
• Ahmad Al-Abdouh, Department of Cardiology, University of Texas Medical Branch at Galveston, Galveston, USA.
• Nada Alrifai, Department of Rheumatology, University of Minnesota, Minneapolis, MN, USA.
• Deaa Abu Jazar, Department of Cardiology, University of Texas Medical Branch at Galveston, Galveston, USA.
• Yasmin Hamdan, Department of Internal Medicine, University of Texas Medical Branch at Galveston, Galveston, USA.
• Mohammed Alsadawi, Department of Cardiovascular Medicine, University of Minnesota, Minneapolis, MN, USA.
• Wissam Khalife, Department of Cardiology, University of Texas Medical Branch at Galveston, Galveston, USA.
• Mukaila Raji, Department of Internal Medicine, Division of Geriatrics and Palliative Medicine, University of Texas Medical Branch at Galveston, Galveston, USA.
• Aiham Albaeni, Department of Cardiology, University of Texas Medical Branch at Galveston, Galveston, USA. Electronic address: [email protected].

Recommended Citation

Obeidat O, Alhuneafat L, Ismail MF, et al. Comparative Effectiveness and Outcomes of Direct Oral Anticoagulants vs. Vitamin K Antagonists (VKA) in Atrial Arrhythmias Patients with Isolated Lupus Anticoagulant Without Antiphospholipid Syndrome: A Real-World Cohort Analysis. Am J Med Sci. Published online August 26, 2026. doi:10.1016/j.amjms.2026.08.019

Affiliations

Advocate Illinois Masonic Medical Center

Abstract

Background: Direct oral anticoagulants (DOACs) are preferred over VKA for stroke prevention in atrial fibrillation/flutter (AF), but concerns exist regarding their use in antiphospholipid syndrome (APS). The safety and effectiveness of DOACs in AF patients with isolated lupus anticoagulant (LA) who do not meet APS criteria remain uncertain.

Methods: Using the TriNetX global research network, we conducted a new-user, active-comparator cohort study of adults with AF/flutter (ICD-10 I48, on or after 2010) and laboratory-documented LA positivity (ICD-10 D68.62 or confirmatory ratio-based dRVVT/lupus-sensitive aPTT assays) established on or before anticoagulant initiation, excluding coded APS (D68.61) and documented positive anticardiolipin or anti-β2-glycoprotein I antibodies. The index date was the first qualifying DOAC or VKA prescription after AF diagnosis. Propensity score matching (1:1) balanced more than 100 covariates including prior stroke/TIA, prior bleeding, prior venous thromboembolism, renal function, and comorbidities. Co-primary outcomes were incident ischemic stroke and incident bleeding at 5 years, analyzed with Kaplan-Meier methods and Cox proportional hazards models.

Results: After matching, 1,152 patients were included (576 per group; mean follow-up ≈2.6 years). Incident ischemic stroke was similar between DOAC and VKA users (5.8% vs. 6.0%; HR 0.93, 95% CI 0.54-1.60; p=0.80). The incident bleeding composite was directionally lower with DOACs without reaching significance (18.0% vs. 22.6%; HR 0.79, 95% CI 0.57-1.10; p=0.17), as were severe intracranial bleeding (2.0% vs. 3.3%; HR 0.61, 95% CI 0.29-1.29) and the intracranial/GI hemorrhage composite (9.1% vs. 12.1%; HR 0.75, 95% CI 0.51-1.12). In a pre-specified full-cohort analysis retaining prior events, the bleeding advantage reached nominal significance (26.6% vs. 33.0%; HR 0.77, 95% CI 0.62-0.95). All-cause mortality did not differ (21.2% vs. 22.0%; HR 0.96, 95% CI 0.75-1.23; p=0.73), and there were no significant differences in myocardial infarction, venous thromboembolism, or composite arterial events. An apixaban-specific analysis was consistent.

Conclusions: In this new-user cohort of AF patients with isolated lupus anticoagulant, DOAC therapy was not associated with higher rates of ischemic stroke, arterial events, venous thromboembolism, or mortality compared with VKA, and bleeding outcomes were directionally lower with DOACs without reaching statistical significance. These hypothesis-generating findings suggest DOACs may be a reasonable option in this population, pending confirmation in prospective studies.

Type

Article

PubMed ID

42648356