Extended Therapy for VTE: Does Anticoagulant Choice Matter?

For those considering extended anticoagulation after initial therapy for venous thromboembolism (VTE), prescription claims databases showed that apixaban (Eliquis) could be a better choice than warfarin.

People prescribed the direct oral anticoagulant (DOAC) had modestly fewer hospitalizations for recurrent VTE (9.8 vs 13.5 per 1,000 person-years, HR 0.69, 95% CI 0.49-0.99) with no change in major bleeding (44.4 vs 47.1 per 1,000 person-years, HR 0.92, 95% CI 0.78-1.09) after propensity score weighting.

Meanwhile, these endpoints suggested no differences between rivaroxaban (Xarelto) and apixaban, nor rivaroxaban and warfarin, for continued therapy after the initial 90 days of oral anticoagulation, according to Katsiaryna Bykov, PharmD, ScD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues, writing in JAMA.

However, they cautioned that the study — an exploratory analysis based on fee-for-service Medicare and two commercial health insurance databases — had limited statistical power to detect any small, but clinically important, differences between these treatments.

Nevertheless, study results persisted in people who had treatment extended past 180 days and those in various subgroups.

“To date, no completed or ongoing randomized clinical trials have directly compared DOACs with warfarin or with each other for extended treatment,” Bykov and colleagues wrote.

“It is unlikely that an adequately powered randomized clinical trial will be conducted that compares all 3 outcomes across at least 3 therapies for extended treatment of patients with VTE. In contrast to the more than 60,000 patients included in this study, the ongoing RENOVE trial will compare full vs reduced doses of DOACs in 2200 participants with unprovoked VTE,” the authors noted.

Guidelines currently recommend at least 3 months of anticoagulation in people with proximal deep vein thrombosis (DVT) or pulmonary embolism (PE). Although DOACs are preferred over vitamin K antagonists in many instances, the limited evidence precludes professional societies from endorsing any specific DOAC for initial or extended treatment in the VTE guidelines.

The retrospective cohort study counted 64,642 adults with a hospitalization for DVT or PE. Patients went into the study regardless of their initial anticoagulation therapy (though most patients continued their initial treatment), and those who had outcomes in the first 90 days were excluded.

Participants were divided into groups based on the oral anticoagulation prescribed beyond the first 90 days after index VTE discharge:

• 9,167 apixaban users (mean age 71, 59.9% women)
• 12,468 rivaroxaban users (mean age 69, 56.7% women)
• 43,007 warfarin users (mean age 70, 59.1% women)

Propensity score weighting yielded balanced groups.

Median follow-up was 109 days for recurrent VTE and 108 days for major bleeding.

Bykov’s group acknowledged that their database lacked important variables such as socioeconomic status, laboratory test results (e.g., international normalized ratio values for patients prescribed warfarin), and prescribed doses of study drugs.