Rivaroxaban was more effective than enoxaparin for preventing venous thromboembolism (VTE) events without increasing bleeding risk in patients immobilized after nonmajor lower limb orthopedic surgery, according to the Late-Breaking Clinical Trial PRONOMOS presented during ACC.20/WCC and simultaneously published in the New England Journal of Medicine.

This international, double-blind, randomized controlled trial is the first to compare oral rivaroxaban against subcutaneous enoxaparin in this moderate-risk population. The noninferiority trial planned to test for superiority if rivaroxaban was shown to be noninferior to enoxaparin. The trial was terminated early in April 2018, because of slower than expected recruitment, which led to reaching expiration dates of the study drugs and the cost to replace them was prohibitively high. The data were blinded at the time of the trial termination.

Researchers studied 3,604 patients from 10 countries who were deemed to be at moderate VTE risk post surgery by the investigator. They were randomized to rivaroxaban 10 mg (1,809 patients) or enoxaparin 4,000 IU (1,795 patients). Their median age was 41 years and two-thirds were men. Overall, patients had a median of 28 days of reduced mobility.

The primary efficacy outcome of major VTE – the composite of symptomatic distal or proximal deep vein thrombosis (DVT), pulmonary embolism, or VTE-related death during the treatment period or asymptomatic proximal DVT at the end of treatment – occurred in four of 1,661 patients (0.2%) in the rivaroxaban group and 18 of 1,640 patients (1.1%) in the enoxaparin group (risk ratio with multiple imputation, 0.25; 95% confidence interval 0.09-0.75; p<0.001 for noninferiority; p=0.01 for superiority).

Bleeding rates did not differ between the rivaroxaban and enoxaparin groups (1.1% and 1.0%, respectively, for major plus nonmajor clinically relevant bleeding; 0.6% and 0.7%, respectively, for major bleeding).

“In Europe, all the guidelines agree that some level of thromboprophylaxis should be given, but overall there is no agreement on what should be done for the patient population who remains at moderate risk for clots because of being immobilized during their recovery,” says Nadia Rosencher, MD, a study author. “This study represents a major step forward in our treatment of patients after many orthopedic procedures because it proves that we can more effectively prevent thrombosis with a once-daily oral medication versus a daily injection with the same safety.”

Clinical Topics: Heart Failure and Cardiomyopathies, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Acute Heart Failure

Keywords: ACC Annual Scientific Session, acc20, Venous Thromboembolism, Venous Thrombosis, Pulmonary Embolism, Hemorrhage, Heart Failure

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