Venous thrombosis recurrence risk according to warfarin versus direct oral anticoagulants for the secondary prevention of venous thrombosis

Neil A. Zakai, Rob F. Walker, Richard F. MacLehose, Insu Koh, Alvaro Alonso, Pamela L. Lutsey

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background: Venous thromboembolism (VTE) affects nearly 1 million Americans annually, and many benefit from continued anticoagulation after the initial 3- to 6-month treatment period (secondary prevention).

Objectives: To determine whether warfarin, apixaban, or rivaroxaban is associated with reduced recurrent VTE hospitalization in the secondary prevention of VTE.

Patients/Methods: We performed a retrospective cohort study of participants enrolled in the MarketScan Insurance Database between 2013 and 2017 in those with an incident VTE. In those individuals who continued oral anticoagulation (warfarin, apixaban, or rivaroxaban) beyond 6 months, we determined the relative rate of recurrent VTE hospitalization.

Results: Among 119 964 individuals with VTE, 25 419 remained on anticoagulation after 6 months and were matched successfully by age, sex, and date. After adjusting for a propensity score, apixaban versus rivaroxaban (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.45-0.94) and apixaban versus warfarin (HR, 0.68; 95% CI, 0.47-1.00) had a reduced risk of recurrent VTE hospitalization, and rivaroxaban versus warfarin (HR, 1.12; 95% CI, 0.94-1.33) had equivalent rates. For the rivaroxaban versus warfarin comparison there was a significant interaction by renal function ( P < .01) where rivaroxaban was associated with a lower risk of recurrent VTE hospitalization (HR, 0.65; 95% CI, 0.41-1.03) in those with kidney disease and increased risk in those without kidney disease (HR, 1.24; 95% CI, 1.02-1.50).

Conclusions: These data suggest that apixaban has a lower recurrent VTE hospitalization rate than rivaroxaban during the secondary prevention of VTE, and further study of diverse patient populations, especially by kidney function, is warranted.

Original languageEnglish (US)
Article numbere12575
JournalResearch and Practice in Thrombosis and Haemostasis
Issue number6
StatePublished - Aug 2021

Bibliographical note

Funding Information:
This study was funded by grants R01HL131579 (PI Lutsey), R01‐HL122200 (PI Alonzo), and K24‐HL148521 (PIA) and from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.

Publisher Copyright:
© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).


  • anticoagulants
  • factor Xa inhibitors
  • secondary prevention
  • venous thromboembolism
  • warfarin


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