DOACs as effective as warfarin for CVT with lower bleeding risk

The risk of recurrent venous thrombosis in patients with cerebral venous thrombosis (CVT) was comparable between those who received warfarin or direct oral anticoagulants (DOACs), according to results of the ACTION-CVT* study presented at ISC 2022.

“In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favourable safety profile when compared to warfarin treatment,” said study lead author Associate Professor Shadi Yaghi, vascular neurology division chief at The Warren Alpert Medical School of Brown University in Providence, Rhode Island, US.

The international, multicentre, retrospective, observational study involved 845 adults (mean age 44.8 years, 64.7 percent female) with CVT who received oral anticoagulant therapy between 2015 and 2020. Of these, 33 percent only received DOACs, 51.8 percent only warfarin, and 15.1 percent received both at different times (crossovers). The most frequently used DOAC was apixaban (66.6 percent), while 18.2 percent received rivaroxaban and 13.5 percent dabigatran. Pregnancy, active cancer, or a history of antiphospholipid antibody syndrome were exclusion criteria.

More patients in the DOAC vs warfarin group had a history of venous thromboembolism (VTE; 15.4 percent vs 6.6 percent), while more patients in the warfarin group had ≥1 antiphospholipid antibody (12.1 percent vs 6.8 percent) or were on low molecular weight heparin (77.9 percent vs 33.3 percent).

Patients were followed up for a median 345 days during which time the rate of recurrent venous thrombosis was 5.68 per 100 patient-years, the rate of major haemorrhage 3.77 per 100 patient-years, and deaths 1.84 per 100 patient-years.

There was no significant difference in the risk of recurrent venous thrombosis** while on oral anticoagulation with DOACs compared with warfarin (5.26 vs 5.87 per 100 patient-years; adjusted hazard ratio [adjHR], 0.94, 95 percent confidence interval [CI], 0.51–1.73; p=0.84). [ISC 2022, abstract LB5; Stroke 2022;doi:10.1161/STROKEAHA.121.037541]

A total of 525 patients were included in the recanalization analysis*** of whom 36.6, 48.2, and 15.2 percent had complete, partial, and no recanalization, respectively.

Rates of partial or complete recanalization were also comparable between patients who were on DOACs or warfarin (adjusted odds ratio, 0.92, 95 percent CI, 0.48–1.73; p=0.79), as was the risk of death (adjHR, 0.78, 95 percent CI, 0.22–2.76; p=0.70).

However, the risk of major haemorrhage was significantly reduced with the use of DOACs compared with warfarin (2.44 vs 4.70 per 100 patient-years; adjHR, 0.35, 95 percent CI, 0.15–0.82; p=0.02). This reduction was primarily due to the decrease in intracranial haemorrhage with DOACs vs warfarin (1.52 vs 3.51 per 100 patient-years), rather than extracranial haemorrhage (0.91 vs 1.15 per 100 patient-years).

CVT, a relatively rare cause of stroke, more often affects younger individuals and women, the latter due to oral contraception and recent childbirth being CVT risk factors, Yaghi said. CVT treatment comprises heparin or fractionated heparin followed by oral anticoagulation.

“[The results show that] for treating CVT patients, both DOACS and warfarin are reasonable options, particularly since even with warfarin, the risk of bleeding is rather low,” said Yaghi.

He noted that the retrospective, observational study design with non-blinded adjudication of outcomes was a limitation. Furthermore, about 16 percent of patients were lost to follow-up and there was a possibility of residual treatment by indication bias.

“Given these study limitations, our findings should be interpreted with caution and require confirmation by large prospective observational studies and clinical trials,” he said, citing the DOAC-CVT and SECRET trials as examples. Additionally, the higher cost associated with DOACs vs warfarin call for research into whether the use of DOACs is cost-effective.