Apixaban May Be More Effective vs Warfarin in Patients with VTE Who Need Extended Anticoagulation

The direct oral anticoagulant was associated with a lower rate of rehospitalization for VTE among patients extending anticoagulation beyond 90 days, investigators report.

Apixaban may be more effective than warfarin to reduce risk of rehospitalization among patients with venous thromboembolism (VTE) who require extended anticoagulation, according to results of a recent retrospective cohort study.

The investigative team from the division of pharmacoepidemiology and pharmacoeconomics at Brigham & Women’s Hospital found that among more than 60 000 patients who filled prescriptions for oral anticoagulants beyond the guideline-recommended period of 90 days, having a prescription dispensed for the factor Xa inhibitor apixaban vs the vitamin K antagonist warfarin had a significant association with a “modestly lower” rate of hospitalization for recurrent VTE; however, there was no significant difference observed between the 2 therapies in the risk of hospitalization for major bleeding nor were there significant differences for comparisons of apixaban vs rivaroxaban and rivaroxaban vs 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.

Current clinical guidelines for managing VTE recommend treatment with an oral anticoagulant for a minimum of 90 days. Citing the limited evidence on an optimal choice for type of anticoagulant for extended therapy, the Brigham and Women’s team, led by Katsiaryna Bykov, PharmD, ScD, conducted an exploratory retrospective 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.

The final study cohort numbered 64 462 adults who had initiated oral anticoagulation following hospitalization for VTE and continued treatment beyond the initial 90 days. Anticoagulant prescriptions across the cohort were distributed as:

Apixaban 9167 patients (mean [SD] age, 71 [14] years; 59.9% women)

Rivaroxaban 12 468 patients (mean age, 69 [14] years; 56.7% women)

Warfarin 43 007 (mean age, 70 [15] years; 59.1% women)

The team’s primary outcomes of interest included hospitalization for recurrent VTE and hospitalization for major bleeding.

Follow-up proceeded from the end of initial 90-day treatment period 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.

Recurrent VTE. After analyses were adjusted using propensity score weighting, the authors report, the incidence rate of hospitalization for recurrent VTE was significantly lower for apixaban vs warfarin (9.8 vs 13.5 per 1000 person-years; hazard ratio [HR], 0.69 [95% CI, 0.49-0.99]), but the incidence rates were not significantly different 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 VTE rehospitalization.

Major bleeding. Rates of hospitalization 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 for warfarin, with resulting 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, and 1.07 (95% CI, 0.93-1.24) for rivaroxaban vs warfarin.

Several important study limitations the authors note that preclude generalization of their findings are related to data missing from the Medicare and 2 commercial health insurance databases and include lack of socioeconomic status, laboratory test results, particularly international normalized ratio values for patients taking warfarin, prescribed doses of study drugs, and mortality rates.


Reference: Pawar A, Gagne JJ, Gopalakrishnan C, et al. Association of type of oral anticoagulant dispensed with adverse clinical outcomes in patients extending anticoagulation therapy beyond 90 days after hospitalization for venous thromboembolism. JAMA. 2022;327(11):1051-1060. doi:10.1001/jama.2022.1920