DOACs Could Lower Bleeding, Hemorrhage Risk vs. Warfarin in Patients with CVT

Shadi Yaghi, MD

Data from the ACTION-CVT study provides evidence demonstrating use of direct oral anticoagulants could be a reasonable alternative to warfarin in patients with cerebral venous thrombosis.

A multicenter international retrospective study including patients form the US, Europe, and New Zealand, results of the study indicate DOAC treatment was associated with a lower risk of major hemorrhage and similar risks of death, recurrent venous thrombosis, and rate of partial/complete recanalization compared with warfarin treatment.

“These findings using real-world data suggest that direct oral anticoagulants are equally as effective as warfarin in reducing the chance of recurrent blood clots and increasing the chance of recanalization, and they have a lower risk of major bleeding,” said lead investigator Shadi Yaghi, MD, vascular neurology division chief at The Warren Alpert Medical School of Brown University in Providence and co-director of the comprehensive stroke center at Rhode Island Hospital, in a statement. “For treating CVT patients, both DOACS and warfarin are reasonable options, particularly since even with warfarin, the risk of bleeding is rather low.”

With mountains of data detailing the antithrombotic effects of DOACs, the role of warfarin versus DOACs has come into question. As such, many studies have been designed to compare the effectiveness of warfarin versus DOACs for multiple conditions, such as atrial fibrillation, pulmonary embolism, and venous thromboembolism. In the wake of a small, randomized trial that found dabigatran may be as effective as warfarin in treatment of cerebral venous thrombosis, the current study, which was presented International Stroke Conference 2022, was designed as an analysis of data from the ACTION-CVT study.

A multicenter retrospective observational study of patients with CVT treated with oral anticoagulation from January 1, 2015-December 31, 2020, at 1 of 27 medical centers in the US, New Zealand, and Europe. A total of 1025 people treated for cerebral venous thrombosis were identified for inclusion. After exclusion of those with cancer, an antiphospholipid antibody syndrome, and those not prescribed oral anticoagulants, investigators were left with a cohort of 845 patients for inclusion in the final analysis.

Efficacy outcomes of interest included recurrent venous thrombosis, which was defined as recurrent venous thromboembolism or recurrent cerebral venous thrombosis. The radiological outcome of interest was complete or partial recanalization and safety outcomes included major hemorrhage and death. Investigators used inverse probability of treatment weighted (IPTW) Cox regression models to compare incidence of outcomes with treatment with warfarin versus treatment with DOACs. For the purpose of analysis, patients who switched from one treatment to another were considered crossovers and adjusted IPTW binary logistic regression was used to compare recanalization rates on follow-up imaging.

These patients had a mean age of 44.8 years, 64.7% were women, and the median follow-up time was 345 (IQR, 140-720) days. 33% received a prescription for a DOAC only, 51.8% received warfarin, and 15.1% were considered crossovers. Of those who received only a DOAC, 66.6% received apixaban, 18.2% received rivaroxaban, 13.5% received dabigatran, and 1.7% received other or multiple.

During the follow-up period, 17 patients experienced recurrent venous thromboembolism, 23 experienced recurrent cerebral venous thrombosis, and 29 experienced a major hemorrhage, with 22 experience g intracerebral hemorrhage and 7 experiencing extracranial hemorrhage. Of the 711 patients who underwent follow-up imaging, 39% had completed recanalization and 46% had partial recanalization.

Upon analysis, results indicated DOAC treatment results in a similar recurrent venous thromboembolism risk (aHR, 0.80 [95% CI 0.43-1.74]; P=.682) and no-recanalization rate on last venous imaging (aOR, 0.76 [95% CI 0.48-1.34]; P=.396) when compared to treatment with warfarin. Conversely, risk of major hemorrhage was nonsignificantly lower in those treated with DOACs. (aHR, 0.45 [95% CI, 0.19-1.05]; P=.065). Investigators also pointed out the risk of recurrent venous thromboembolism was greater among those with prior venous thromboembolism (aHR, 2.20 [95% CI, 0.93-5.22]) and those with at least 1 positive antiphospholipid antibody (aHR, 2.81 [95% CI, 1.26-6.23]).

This study, “Direct Oral Anticoagulants Versus Warfarin In The Treatment Of Cerebral Venous Thrombosis (ACTION-CVT): A Multi-Center International Study,” was presented at ISC 2022.