Rivaroxaban Benefit in CAD, PAD Stops Huge Randomized Trial

February 09, 2017

BERLIN, GERMANY — A daily antithrombotic regimen containing rivaroxaban (Xarelto, Bayer/Janssen) fared significantly better than aspirin alone for the primary end point in a massive randomized clinical-outcomes trial of patients with CAD or peripheral artery disease (PAD), according to company announcements[1,2].

The phase 3 Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial was halted more than a year ahead of its planned March 2018 completion because, in an interim analysis, the primary end point of MI, stroke, or cardiovascular death "has reached its prespecified criteria for superiority." In their press releases with superficial top-line COMPASS results, the companies did not discuss the other primary end point of major bleeding.

The trial had randomized 27,402 patients at hundreds of sites around the world to receive the direct oral anticoagulant (DOAC) rivaroxaban at 2.5 mg twice daily plus aspirin at 100 mg/day, or rivaroxaban 5 mg twice daily without aspirin, or aspirin 100 mg/day without rivaroxaban.

The companies do not say which rivaroxaban-containing regimen was superior for the primary end point. Dr Stuart J Connolly (McMaster University, Hamilton, ON) would tell heartwire from Medscape only "that at least one of the rivaroxaban-based arms was superior to aspirin alone." Connolly is on the executive committee of his center's Population Health Research Institute (PHRI), which played a lead role in the trial.

The companies say the trial's complete results are expected to be presented at a meeting later in 2017, but for now, "owing to the magnitude of effect and the confirmation of the existing safety profile of rivaroxaban," its patients will be offered the drug in an open-label extension trial.

COMPASS excluded patients with an indication for dual antiplatelet therapy, nonaspirin antiplatelets, or oral anticoagulants or those with a stroke within 30 days, a hemorrhagic stroke at any time, or heart failure worse than NYHA class 2.

While aspirin is a mainstay for high-risk patients with documented peripheral and/or coronary artery disease, a switch to or the addition of a DOAC would represent a major shift in practice in some countries. The drugs are frequently prescribed in patients with nonvalvular atrial fibrillation, while rivaroxaban itself is also approved for treatment or prevention of deep-vein thrombosis and peripheral thromboembolism. It's approved with antiplatelets for acute coronary syndromes in Europe but isn't approved for that indication in the US.

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