Major Bleed Risk Higher With Warfarin Than Xarelto in CTEPH Patients, Study Finds

Among people with chronic thromboembolic pulmonary hypertension (CTEPH), certain anticoagulants may reduce the risk of serious bleeding more than others, a new study shows.

The study, “Real-life data of direct anticoagulant use, bleeding risk and venous thromboembolism recurrence in chronic thromboembolic pulmonary hypertension patients: an observational retrospective study,” was published recently in the journal Pulmonary Circulation.

CTEPH is caused by the formation of blood clots within vessels of the lungs. That’s why treatment with anticoagulants (medications that stop blood from clotting) is a cornerstone of CTEPH treatment.

Such medications include warfarin (brand names Coumadin, Jantoven) and rivaroxaban (brand name Xarelto). Broadly, these therapies work by blocking the activity of clotting proteins in the blood, though the specific proteins affected varies depending on the medication taken.

Despite the importance of anticoagulants in CTEPH treatment, relatively little is known about their effectiveness and safety in this patient population.

Researchers reviewed clinical data from 501 people with CTEPH who were treated at their institution in Turkey, from September 2011 to April 2018. The goal was to determine preferences regarding oral anticoagulant use, as well as their safety and effectiveness. Bleeding risk, venous thromboembolism recurrence, and death events also were assessed.

The group analyzed was 50.7% female, and the average age was 53.54 years. Participants were followed for an average of nine years.

Most individuals (412, 82.2%) were initially prescribed warfarin, though 100 (24.2%) of these switched to other therapies over the follow-up period. The most common reasons for switching were bleeding events, and elevated International Normalized Ratio (INR) — a standardized measure reflective of the blood’s clotting ability; high INR values suggest an increased risk of bleeding.

In the group analyzed, after eventual switches, warfarin and Xarelto were the most commonly used anticoagulants, in 312 and 134 participants, respectively. As such, researchers compared the safety profiles of these two medications.

Results showed no significant differences between warfarin and Xarelto in terms of overall survival rate — all-cause mortality rates were 13.8% in the warfarin group, and 9.7% in the Xarelto group.

Rates of overall bleeding events or recurrent venous thromboembolism (a dangerous condition in which clots form in the bloodstream and get “stuck” in the lungs), also were not significantly different between the two medications.

However, major bleeding episodes were significantly more common in those taking warfarin: 14.8% compared with 8.9% in those taking Xarelto. This translates to a roughly doubled risk of serious bleeding episodes on warfarin, relative to Xarelto.

Consistently, while overall survival did not differ between groups, individuals on warfarin were significantly more likely to die due to bleeding (mortality rate of 4.85%) than those on Xarelto (mortality rate of 2.2%).

“The main difference [between the two anticoagulants] was found with major bleeding that was mainly associated with the death rate related to major bleeding,” the researchers wrote.

The results suggested that Xarelto or similar oral anticoagulants “would be a more reasonable way of preventing bleeding events without increasing thromboembolic risk” in people with CTEPH. Additional research — in particular, prospective, randomized, clinical trials — will be needed to validate these results, they noted.