Extended Apixaban Treatment Associated With Lower VTE Hospitalization Rate

Katsiaryna Bykov, PharmD, ScD

New findings suggest prescription dispenses for apixaban compared with warfarin had significant associations with lower rates of hospitalization for recurrent venous thromboembolism (VTE), but no significant difference in the rate of hospitalizations for major bleeding.

Investigators in the recent exploratory analysis also found no significant differences for comparisons of apixaban versus rivaroxaban or rivaroxaban versus warfarin in either outcome for comparison of extended treatment beyond 90 days.

“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 study author Katsiaryna Bykov, PharmD, ScD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School.

A total of 3 health care claims databases with data on individuals in the US who had public (fee-for-service Medicare from January 2009 - December 2017) and commercial (Optum Clinformatics Data Mart and IBM MarketScan from January 2004 - December 2018) health care insurance were identified and used.

In each database, investigators identified patients who filled a prescription for an oral anticoagulant (index therapy) within 30 days after index VTE discharge and who completed the initial treatment episode of 90 days.

Then, in order to identify those who extended treatment beyond 90 days, investigators identified patients that had a prescription dispensing for apixaban, rivaroxaban, or warfarin that ended within days 84 - 104 after initiation of the index therapy and filled a subsequent prescription within 14 days at the end of that treatment episode.

The primary outcomes included hospitalizations for recurrent VTE and hospitalization for major bleeding. In the analyses, patients were followed up with until the first occurrence of treatment cessation, outcome occurrence, health plan disenrollment, death, or end of available data.

Investigators identified 9,167 patients prescribed apixaban (mean age, 71 years; 59.9% women), 12,468 patients prescribed rivaroxaban (mean age, 69 years; 56.7% women), and 43,007 patients prescribed warfarin (mean age, 70 years; 59.1% women).

Data show the median follow-up was 109 days for recurrent VTE and 108 days for major bleeding hospitalization outcomes.

The weighted rates of hospitalization for recurrent VTE were 9.8 (95% CI, 6.8 - 13.6) per 1000 person-years in the apixaban group, 11.6 (95% CI, 8.5 - 15.4) per 1000 person-years in the rivaroxaban group, and 13.5 (95% CI, 10.2 - 17.6) per 1000 person-years in the warfarin group.

Investigators noted the incidence rate for recurrent VTE was significantly lower for apixaban compared with warfarin (hazard ratio [HR] 0.69, [95% CI, 0.49 - 0.99]). However, the incidence rates were not statistically different between apixaban and rivaroxaban (HR, 0.80 [95% CI, 0.53 - 1.19]) or rivaroxaban and warfarin (HR, 0.87 [95% CI, 0.65 - 1.16]).

The rates of hospitalizations for major bleeding were 44.4 per 1000 person-years for apixaban, 50.0 per 1000 person-years for rivaroxaban, and 47.1 per 1000 person-years. Investigators observed HRs of:

• 0.92 (95% CI, 0.78-1.09) for apixaban vs warfarin
• 0.86 (95% CI, 0.71-1.04) for apixaban vs rivaroxaban
• 1.07 (95% CI, 0.93-1.24) for rivaroxaban vs warfarin.

The 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.