Apixaban reduces bleeding risk versus rivaroxaban in acute venous thromboembolism

1. In a randomized controlled trial of patients with acute venous thromboembolism, apixaban was associated with a substantially lower risk of clinically relevant bleeding compared with rivaroxaban.

2. Rates of recurrent venous thromboembolism and death were similar between groups, suggesting comparable efficacy despite differences in safety.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Venous thromboembolism (VTE) is a common and potentially fatal cardiovascular condition, ranking among the leading causes of cardiovascular morbidity and mortality worldwide. Direct oral anticoagulants (DOACs) such as apixaban (Eliquis) and rivaroxaban (Xarelto) are widely used first-line therapies due to ease of use and favorable safety compared with older agents, yet there is a lack of high-quality head-to-head data to guide drug selection. This randomized trial addressed that gap by directly comparing apixaban and rivaroxaban in patients with acute symptomatic VTE. Over the three-month treatment period, apixaban demonstrated a markedly lower risk of clinically relevant bleeding, including both major and nonmajor bleeding events. Importantly, this safety advantage did not come at the cost of efficacy, as recurrence of VTE and mortality outcomes were similar between groups. Strengths of the study include its randomized design, pragmatic international enrollment, and blinded outcome adjudication, which enhance internal validity and generalizability. However, limitations should be considered. The open-label design introduces potential bias, although objective bleeding outcomes mitigate this concern. The follow-up duration was limited to the early treatment phase, leaving longer-term comparative safety uncertain. Additionally, certain populations—such as patients with cancer, severe obesity, or diverse racial backgrounds—were underrepresented, limiting applicability to these groups. Overall, this study demonstrated that apixaban had comparable efficacy and a superior safety profile compared to rivaroxaban in the treatment of acute VTE.

Click to read the study in NEJM

Relevant Reading: Apixaban for Extended Treatment of Provoked Venous Thromboembolism

In-Depth [randomized controlled trial]: This study was an international, prospective, randomized controlled trial comparing apixaban and rivaroxaban for the treatment of acute symptomatic venous thromboembolism (VTE), including pulmonary embolism and proximal deep-vein thrombosis. A total of 2760 patients were randomized in a 1:1 ratio to receive either apixaban (10 mg twice daily for 7 days followed by 5 mg twice daily) or rivaroxaban (15 mg twice daily for 21 days followed by 20 mg daily) for a 3-month treatment period. The primary outcome was clinically relevant bleeding, defined as a composite of major bleeding and clinically relevant nonmajor bleeding per International Society on Thrombosis and Haemostasis criteria. In the intention-to-treat analysis, the primary outcome occurred in 3.3% of patients in the apixaban group compared to 7.1% in the rivaroxaban group (relative risk [RR], 0.46; 95% confidence interval [CI], 0.33 to 0.65; p<0.001). Major bleeding events were notably lower with apixaban (0.4% vs. 2.4%; RR, 0.16; 95% CI, 0.06 to 0.40), while clinically relevant nonmajor bleeding was also reduced (2.9% vs. 4.9%; RR, 0.59; 95% CI, 0.40 to 0.86). Despite this difference in safety outcomes, efficacy appeared similar between groups. Recurrent symptomatic VTE occurred in 1.1% of patients receiving apixaban and 1.0% receiving rivaroxaban (RR, 1.08; 95% CI, 0.52 to 2.23). All-cause mortality was low and comparable (0.1% vs. 0.3%). These findings suggest that apixaban maintained equivalent effectiveness while offering a superior bleeding profile. Kaplan–Meier curves demonstrated early separation in bleeding risk between groups, raising the possibility that the higher initial dosing phase of rivaroxaban contributed to the increased bleeding risk observed. Overall, this trial provided high-quality evidence that apixaban reduced clinically relevant bleeding compared to rivaroxaban without compromising efficacy in the short-term treatment of acute VTE.

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