Apixaban or Rivaroxaban for VTE?
Hey Team,
Question: Should I be prescribing Apixaban (Eliquis) or Rivaroxaban for venous thromboembolism?
Background: Both apixaban and rivaroxaban are direct factor Xa inhibitors—they block Xa in the coagulation cascade, preventing conversion of prothrombin to thrombin and reducing clot formation. The main difference is pharmacokinetics. Apixaban is dosed twice daily with more stable plasma levels while rivaroxaban is dosed once daily and therefore has a bit more of a peak and trough.
At this time, we have no published, direct, head-to-head RCTs for apixaban vs rivaroxaban. There are several trials underway, but based on clinicaltrials.gov, these are likely several years away. So where does that leave us?
We have several observational/cohort studies and a couple of meta-analyses to go off of at this point (and a mixed bag of Afib and VTE indications)
A meta‐analysis of patients being treated with AC for non-valvular atrial fibrillation for stroke prevention found that apixaban was associated with lower rates of major bleeding compared with rivaroxaban (HR ~0.62; 95% CI 0.56-0.69) and lower rates of GI bleeding (HR ~0.57; 95% CI 0.50-0.64) with no loss of efficacy compared with rivaroxaban.1
Another large Medicare‐based cohort (patients ≥65 years with atrial fibrillation) found treatment with rivaroxaban compared with apixaban was associated with a significantly increased risk of major ischemic or hemorrhagic events. (16.1 vs 13.4 per 1000 person‐years; HR ~1.18).2
Check out this EMDOCS 52 in 52 post on this study.
A VTE meta‐analysis found for apixaban vs rivaroxaban a significantly decreased risk of major bleeding when using apixaban, RR ~0.68 (95% CI 0.61-0.76), with a trend towards lower risk of recurrent VTE with apixaban compared to rivaroxaban (RR 0.77, 95% CI 0.57-1.04).3
Another population-based cohort study looking at patients with VTE had lower rates for recurrent VTE and bleeding in those newly starting apixaban than rivaroxaban.4
Check out this EMA Episode covering this study
Another registry-based cohort study looked at outcomes with apixaban, rivaroxaban, and warfarin for Afib and/or VTE. They observed that bleeding was highest with rivaroxaban, followed by warfarin, and then apixaban. Rates of thrombosis were similar between rivaroxaban and apixaban.5
Without an RCT, where does that leave us?
If the patient is older, has prior GI disease, CKD, or will be on interacting drugs, the real-world data lean toward apixaban to reduce bleeding risk without giving up efficacy.
If adherence is a serious worry and once-daily dosing is the make-or-break factor, rivaroxaban can be reasonable, but counsel hard on bleeding risk.
References
Mamas, M. A., Batson, S., Pollock, K. G., Grundy, S., Matthew, A., Chapman, C., Manuel, J. A., Farooqui, U., & Mitchell, S. A. (2022). Meta-Analysis Comparing Apixaban Versus Rivaroxaban for Management of Patients With Nonvalvular Atrial Fibrillation. The American journal of cardiology, 166, 58–64. [pubmed]
Ray, W. A., Chung, C. P., Stein, C. M., Smalley, W., Zimmerman, E., Dupont, W. D., Hung, A. M., Daugherty, J. R., Dickson, A., & Murray, K. T. (2021). Association of Rivaroxaban vs Apixaban With Major Ischemic or Hemorrhagic Events in Patients With Atrial Fibrillation. JAMA, 326(23), 2395–2404. [pubnmed]
Fredman, D., McNeil, R., Eldar, O., Leader, A., Gafter-Gvili, A., & Avni, T. (2024). Efficacy and safety of rivaroxaban versus apixaban for venous thromboembolism: A systematic review and meta-analysis of observational studies. Journal of thrombosis and thrombolysis, 57(3), 453–465. [pubmed]
Dawwas, G. K., Leonard, C. E., Lewis, J. D., & Cuker, A. (2022). Risk for Recurrent Venous Thromboembolism and Bleeding With Apixaban Compared With Rivaroxaban: An Analysis of Real-World Data. Annals of internal medicine, 175(1), 20–28. {pubmed]
Schaefer JK, Errickson J, Kong X, et al. A Comparison of Outcomes With Apixaban, Rivaroxaban, and Warfarin for Atrial Fibrillation and/or Venous Thromboembolism. JACC Adv. 2025;4(5):101714. [pubmed]
