Patients with thrombotic antiphospholipid syndrome (APS) who receive direct oral anticoagulants (DOACs) may have an increased risk for arterial thrombosis compared with those who receive vitamin-K antagonists (VKAs), according to a study in the Journal of the American College of Cardiology.
Researchers conducted a systematic review and meta-analysis after searching PubMed, EMBASE, and the Cochrane Central Register of Clinical Trials for randomized controlled trials (RCTs) through April 9, 2022, as well as ClinicalTrials.gov for any ongoing trials. Eligible RCTs included patients aged older than 18 years with thrombotic APS and reported cardiovascular outcomes in those receiving DOACs vs VKAs.
The main efficacy outcomes were a composite of arterial thrombotic events and venous thromboembolic events (VTE). The main safety outcome was major bleeding based on the definition of the International Society on Thrombosis and Hemostasis.
A total of 4 RCTs with 474 patients (234 patients assigned to DOACs and 240 patients assigned to VKAs) were included. Participants had an average age of 48.0 years, 68% were women, and their mean body mass index was 28.3. The mean percent time in the therapeutic range for patients who received VKAs was 60%, and the mean follow-up was 19 months.
Use of DOACs vs VKAs was associated with increased odds of the composite of arterial thrombotic events (10.3% vs 1.3%; odds ratio [OR], 5.43; 95% CI, 1.87-15.75; P <.001; I2=0%). The odds of having a subsequent stroke were significantly higher for participants who received DOACs compared with those who received VKAs (8.6% vs 0%; OR, 10.74; 95% CI, 2.29-50.38; P <.001; I2=0%).
The odds of VTE risk were not significantly different between participants in the DOAC group compared with those in the VKA group (1.7% vs 1.3%; OR, 1.20; 95% CI, 0.31-4.55; P =.79; I2=0%). The odds of major bleeding were not significantly different between participants who received DOACs compared with those who received VKAs (4.3% vs 4.2%; OR, 1.02; 95% CI, 0.42- 2.47; P =.97; I2=0%).
Use of DOACs was associated with increased odds of the composite outcome of arterial thrombotic events or VTE compared with use of VKAs (11.5% vs 2.5%; OR, 4.46; 95% CI, 1.12-17.84; P =.03; I2=0%). All-cause mortality was not significantly different between participants who received DOACs vs those who received VKAs (2.6% vs 1.7%; OR, 1.43; 95% CI, 0.44-4.62; P =.55, I2=0%).
In a subgroup analysis of participants with different types of thrombotic APS, those who received DOACs vs VKAs had increased odds of a composite of arterial thrombotic events and no change in the odds of subsequent VTE or major bleeding based on whether they had triple APS or another APS combination. No statistically significant subgroup effect was found in outcomes (P =.80 for arterial thrombotic events, P =.85 for VTE, and P =.45 for major bleeding).
Study limitations include the number of included studies is small and sample size is pooled. In addition, analysis is observational and rivaroxaban and apixaban were not compared with each other.
“Collectively, the findings of this study do not support the routine use of existing DOAC regimens in patients with thrombotic APS,” the investigators wrote. “Further RCTs will be required to elucidate whether higher doses of DOACs can offer convenience to patients and clinicians, while ensuring efficacy and safety.”
Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
This article originally appeared on The Cardiology Advisor
Khairani CD, Bejjani A, Piazza G, et al. Direct oral anticoagulants vs vitamin-K antagonists in thrombotic antiphospholipid syndrome: meta-analysis of randomized controlled trials. J Am Coll Cardiol. Published online October 31, 2022. doi: 10.1016/j.jacc.2022.10.008