DOACs Comparable to Warfarin in CVT

February 15, 2022

Use of direct oral anticoagulant drugs (DOACs) appears to be just as effective as warfarin in preventing future thrombotic events in patients with cerebral venous thrombosis (CVT) stroke, and are less likely to result in major bleeding, a retrospective study suggests.

The ACTION CVT study was presented on February 10 at the International Stroke Conference (ISC) 2022 by Ekaterina Bakradze, MD, assistant professor of neurology at the University of Alabama at Birmingham.

It was also simultaneously published online in Stroke.

"This real-world data supports use of direct oral anticoagulant drugs as a reasonable alternative to warfarin in patients with cerebral venous thrombosis," Bakradze concluded.

But she added that because this study was based on retrospective observational data, the findings should be interpreted with caution and require confirmation by larger prospective studies.

Two such studies are now underway: the Direct Oral Anticoagulants in the Treatment of Cerebral Venous Thrombosis (DOAC-CVT) study and the randomized Study of Rivaroxaban for Cerebral Venous Thrombosis (SECRET) trial.

Bakradze explained that cerebral venous thrombosis is a less common cause of stroke and occurs more often in women and younger patients, with a median age of 37 years. Current recommended treatment consists of heparin followed by oral anticoagulation.

She noted that although randomized trials and current guidelines indicate that DOACs are a preferred alternative to warfarin for the treatment of patients with venous thromboembolism, there are limited data on their use in patients with CVT.

A small, randomized trial (RESPECT-CVT) showed no significant difference in efficacy and safety outcomes between dabigatran and warfarin in patients with cerebral venous thrombosis, but with only 120 patients, this trial was too small for definite answers to this question.

A better understanding of this issue is important because the mechanisms underlying cerebral venous thrombosis and other thromboembolism and their subsequent risks may differ, Bakradze said.

As randomized trials in patients with cerebral venous thrombosis are difficult to perform because the condition has a low incidence and low event rates, the researchers decided to look at this question with a large retrospective multicenter study.

The ACTION-CVT study involved 845 consecutive patients with cerebral venous thrombosis over 6 years (from January 2015 and December 2020) from 27 centers in Italy, New Zealand, Switzerland, and the United States. Patients were identified from medical records with diagnostic codes and confirmed with imaging.

The primary predictor in the study was oral anticoagulant type (DOAC vs warfarin). Study outcomes were abstracted by individual sites through review of all available medical records.

The primary outcome was recurrent venous thrombosis (venous thromboembolism or cerebral venous thrombosis) during follow-up. Imaging outcomes based on recanalization status on last venous imaging study abstracted from radiology reports were also reported.

The safety outcome was major hemorrhage, defined as new or worsening intracranial hemorrhage (ICH), or major extracranial hemorrhage. Results were adjusted for age, sex, and relevant medical conditions.

The mean age of the patients included was 44.8 years, 64.7% were women, 33% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times.

Results showed that during a median follow-up of 345 days, there were 5.68 recurrent venous thrombosis events, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years.

Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization.

When compared with warfarin, DOAC treatment was associated with similar risk for recurrent venous thrombosis (adjusted hazard ratio [aHR], 0.94; 95% CI, 0.51 - 1.73; P = .84), death (aHR, 0.71, 95% CI, 0.24 - 2.08; P = .53), and rate of partial/complete recanalization (adjusted odds ratio, 0.92, 95% CI, 0.48 - 1.73; P = .79).

But patients who received a DOAC had a significantly lower rate of major hemorrhage (aHR, 0.35; 95% CI, 0.15 - 0.81; P = .02).

When examined separately, the occurrence of ICH per 100 patient-years was much lower among the patients prescribed DOACs than those who were prescribed warfarin (1.52 vs 3.51), whereas the occurrence of major bleeding outside the brain was similar (0.91 vs 1.15).

Commenting on the study at an ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association, and professor of neurology at Columbia University, New York City, said: "The community has been concerned about extending the use of these new direct-acting oral anticoagulant drugs to cerebral venous thrombosis, but this study suggests that these patients may benefit from these new agents too."

Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, also commented: "This study confirms what we already know from other indications about these DOAC drugs: that they have similar efficacy to warfarin but a better safety profile. These results are really spot on with that. These drugs are also much easier and more convenient to use than warfarin.

"This is a great step forward," he added. "Only 30% of patients in this study received DOACs, reflecting the fact that clinicians may be a little reluctant to use them in this condition. But this study now has the potential to change practice."

In an editorial accompanying the publication in Stroke, Johnathon Gorman, MD, and Thalia Field, MD, from the Vancouver Stroke Program at the University of British Columbia, say that despite its methodological limitations, the ACTION-CVT study "provides added value to the current state of knowledge by virtue of its size and 'real world' setting that is reflective of how DOACs are being used to manage CVT in current clinical practice."

They point out that although baseline characteristics between the DOAC and warfarin groups were similar, the possibility of confounding cannot be excluded, and "other characteristics not easily captured in a retrospective study may sway anticoagulation strategy."

They acknowledge, however, that an additional propensity score analysis "provides reassurance that the groups are reasonably balanced, adjusting for variables associated with recurrent cerebral venous thrombosis, recanalization, and hemorrhage."

The editorialists conclude that ACTION-CVT gives additional reassurance for DOACs as an alternative approach to warfarin as a treatment for cerebral venous thrombosis and for the shifts in clinical practice that are already occurring at many centers.

The study was partially supported by the Italian Ministry of Health Ricerca Corrente–IRCCS MultiMedica. Bakradze reports no disclosures. Field is the principal investigator of the SECRET trial, which received in-kind study medication from Bayer Canada. She reports honoraria from HLS Therapeutics outside the submitted work and is on the board of Destine Health. The other editorialist reports no conflicts.

International Stroke Conference (ISC) 2022: Abstract LBS5. Presented February 10, 2022.

Stroke. Published online February 10, 2022. Full text, Editorial

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