Longer dosages of apixaban vs. warfarin linked to lower recurrent VTE hospitalization rate
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Prescriptions dispensed for apixaban beyond 90 days after hospitalization resulted in a lower rate of hospitalization for recurrent venous thromboembolism compared with warfarin beyond 90 days, according to study results published in JAMA.
However, researchers observed no significant differences in risk for hospitalization for major bleeds and no significant differences for comparisons between apixaban vs. rivaroxaban and rivaroxaban vs. warfarin.
Rationale and methods
“Guidelines for managing VTE recommend at least 90 days of therapy with oral anticoagulants. Limited evidence exists about the optimal drug for continuing therapy beyond 90 days,” Katsiaryna Bykov, PharmD, ScD, researcher in the division of pharmacoepidemiology and pharmacoeconomics in the department of medicine at Brigham and Women’s Hospital and Harvard Medical School, and colleagues wrote.
Researchers conducted an exploratory retrospective cohort study of 64,642 patients included in fee-for-service Medicare between 2009 and 2017 and in two commercial health insurance databases between 2004 and 2018.
Patients initiated oral anticoagulation after hospitalization discharge for VTE and continued on treatment beyond 90 days with apixaban (Eliquis, Bristol Myers Squibb/Pfizer; n = 9,167; mean age, 71 years; 59.9% women), rivaroxaban (Xarelto, Janssen Pharmaceuticals; n = 12,468; mean age, 69 years; 56.7% women) or warfarin (n = 43,007; mean age, 70 years; 59.1% women).
Hospitalization for recurrent VTE and for major bleeding served as primary outcomes. Researchers followed patients through to the end of initial 90-day treatment episode until treatment cessation, outcome, mortality, unenrollment or end of available data.
Median follow-up was 109 days for recurrent VTE and 108 days for major bleeding.
Key findings
Patients assigned apixaban had significantly lower incidence rates of hospitalization for recurrent VTE vs. those assigned warfarin (9.8 per 1,000 person years vs. 13.5 per 1,000 person years; HR = 0.69; 95% CI, 0.49-0.99).
Conversely, researchers did not observe significant differences in incidence rates between apixaban vs. rivaroxaban (9.8 per 1,000 person years vs. 11.6 per 1,000 person years; HR = 0.8; 95% CI, 0.53-1.19) or rivaroxaban vs. warfarin (HR = 0.87; 95% CI, 0.65-1.16).
Researchers reported hospitalization rates for major bleeding of 44.4 per 1,000 person years with apixaban, 50 per 1,000 person years with rivaroxaban and 47.1 per 1,000 person years with warfarin. These rates corresponded to HRs of 0.92 (95% CI, 0.78-1.09) with apixaban vs. warfarin, 0.86 (95% CI, 0.71-1.04) with apixaban vs. rivaroxaban and 1.07 (95% CI, 0.93-1.24) with rivaroxaban vs. warfarin.
Implications
The findings are generalizable to people who are event-free and who continue receiving anticoagulation therapy after 90 days of treatment regardless of initial anticoagulation therapy, according to Bykov and colleagues.
“Although this study assessed the comparative effectiveness and safety of oral anticoagulants beyond the initial 90 days of anticoagulation therapy, the overall comparative risk-benefit of oral anticoagulants in patients with VTE depends, in part, on outcomes that occurred during the first 3 months of treatment but outcomes during the first 3 months of therapy were not considered in this study,” they wrote.
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