Apixaban Could Offer Improved Outcomes vs Warfarin in Patients with VTE Requiring Extended Anticoagulation

Katsiaryna Bykov, PharmD, ScD

New data from a Brigham and Women’s Hospital-led team provides an overview of the impact of oral anticoagulant type on clinical outcomes in patients with venous thromboembolism (VTE) extending anticoagulation therapy beyond 90 days after hospitalization.

An exploratory retrospective cohort study including data from more than 64,000 patients, results of the study suggest apixaban prescription dispenses after 90 days were associated with a modest reduction in rate of hospitalization for recurrent VTE, but no significant difference in rate of hospitalization for major bleeding compared to warfarin or in comparisons of apixaban against rivaroxaban or rivaroxaban against warfarin.

“Results from this investigation provide some evidence that extending treatment after 90 days with apixaban vs warfarin may be beneficial. More data are needed for definitive conclusions about the relative benefits and risks of apixaban compared with rivaroxaban and of rivaroxaban vs warfarin, because this study had limited statistical power to detect small, but clinically important, differences between these treatments,” wrote investigators.

Although major guidelines recommended at least 90 days of anticoagulant therapy for patients with VTE, a team led by Katsiaryna Bykov, PharmD, ScD, of the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital, conducted the current study to address the limited evidence gap related to outcomes associated with anticoagulant type beyond 90 days. To do so, Bykov and team designed their study as an exploratory retrospective cohort study using data from fee-for-service Medicare beneficiaries between 2009-2017 and from the Optum Clinformatics Data Mart and IBM MarketScan databases from 2004-2018.

From these data sources, investigators identified a cohort of 64,642 adult patients who initiated anticoagulation following hospitalization discharge for VTE and continued use beyond 90 days. This included 9167 patients prescribed apixaban (mean [SD] age, 71 [14] years; 5491 [59.9%] women), 12.468 patients prescribed rivaroxaban (mean age, 69 [14] years; 7067 [56.7%] women), and 43,007 patients prescribed warfarin (mean age, 70 [15] years; 25 404 [59.1%] women).

Investigators designed propensity score-weighted analyses to assess primary outcomes, which were hospitalization for recurrent VTE and hospitalization for major bleeding. These outcomes were assessed beginning at the end of the initial 90-day treatment episode through treatment cessation, outcome, death, disenrollment, or end of available data. The median follow-up was 109 (IQR, 59-228) days for the recurrent VTE outcome and 108 (IQR, 58-226) days for the bleeding outcome.

In the investigators’ analysis, results suggested the incidence rate of hospitalization for recurrent VTE was significantly lower with apixaban than with warfarin (9.8 vs 13.5 per 1000 person-years; HR, 0.69 [95% CI, 0.49-0.99]), but no significant differences were observed between apixaban and rivaroxaban (9.8 vs 11.6 per 1000 person-years; HR, 0.80 [95% CI, 0.53-1.19]) or rivaroxaban and warfarin (HR, 0.87 [95% CI, 0.65-1.16]) for the recurrent VTE outcome.

When assessing rates of hospitalization for major bleeding, rates were 44.4 per 1000 person-years for apixaban, 50.0 per 1000 person-years for rivaroxaban, and 47.1 per 1000 person-years for warfarin. Based on these results, investigators determined there were no significant differences observed for rates of bleeding for apixaban and warfarin (HR, 0.92 [95% CI, 0.78-1.09]), apixaban and rivaroxaban (HR, 0.86 [95% CI, 0.71-1.04]), and rivaroxaban and warfarin (HR, 1.07 [95% CI, 0.93-1.24]).

Investigators underlined 7 specific limitations within their study for clinicians to consider when interpreting findings. These included inability to assess doses of study drugs, reliance on claims-based data, and lack of mortality data for patients within the Optum Clinformatics Data Mart and IBM MarketScan databases.

This study, “Association of Type of Oral Anticoagulant Dispensed With Adverse Clinical Outcomes in Patients Extending Anticoagulation Therapy Beyond 90 Days After Hospitalization for Venous Thromboembolism,” was published in JAMA.