FDA Approves Rivaroxaban Indication for the Reduction of Major Cardiovascular Events

The US Food and Drug Administration (FDA) has updated the labeling for Johnson and Johnson’s Xarelto (rivaroxaban). The updated label notes that rivaroxaban is indicated to reduce the risk of major cardiovascular events, including cardiovascular (CV) death, myocardial infarction, and stroke in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD).

The blood thinner already had indications for reducing the risk of stroke and systemic embolism in certain patients, treating deep vein thrombosis and pulmonary embolism, and preventing deep vein thrombosis in patients undergoing joint replacement surgeries.

"Despite the use of guideline-recommended therapies, patients with chronic CAD and/or PAD remain at risk of having a devastating and irreversible CV event," said Paul Burton, MD, PhD, FACC, Vice President, Medical Affairs, Internal Medicine, Janssen Scientific Affairs, LLC. "The new Xarelto vascular 2.5-mg dose, when used with aspirin, represents a true breakthrough for patients with chronic CAD and PAD."

The recommended dosage for this new indication is rivaroxaban 2.5 mg twice daily in addition to 75-100 mg of aspirin once daily. Rivaroxaban tablets may be taken with or without food. If a dose is missed, the patient should take a single 2.5 mg dose of rivaroxaban at the next scheduled time.

"Treating patients with aspirin only is simply not enough to address the underlying thrombotic risk that comes with chronic CAD and PAD," said Kelley Branchi, MD, MSc, FACC, FSCCT, Associate Professor in Cardiology, University of Washington, Seattle. "As we saw in the COMPASS trial, the dual pathway approach of aspirin and the 2.5-mg, twice-daily dose of Xarelto can help significantly reduce the risk of CV events in these populations."

Data from the COMPASS trial of rivaroxaban in patients with peripheral artery disease showed that rivaroxaban in conjunction with aspirin reduced the risk of major cardiovascular events by 24%. Specifically, rivaroxaban with aspirin provided a 42% reduction in stroke, 22% reduction in CV death, and 14% reduction in heart attack compared to aspirin alone.

In COMPASS, a total of 27,395 participants with CAD or PAD were randomized (1:1:1) to rivaroxaban 2.5 mg orally twice daily plus aspirin 100 mg once daily, rivaroxaban 5 mg orally twice daily alone, or aspirin 100 mg once daily alone. Rivaroxaban 5 mg was not found to be superior or aspirin alone.

A benefit-risk analysis compared the number of cardiovascular events prevented to the number of fatal or life-threatening bleeding events in the rivaroxaban plus aspirin group versus the aspirin only group. Over 10,000 patient-years of treatment, the study found that the combination therapy would result in 70 fewer cardiovascular events and 12 additional life-threatening bleeding events.

Rivaroxaban continues to come with a boxed warning about the increased risk of thrombotic events with the premature discontinuation of the drug. Additionally, the boxed warning states that epidural or spinal hematomas have occurred in patients taking rivaroxaban who are receiving neuraxial anesthesia or undergoing spinal puncture.

Rivaroxaban can cause serious and even fatal bleeding. Earlier this year andexanet alfa (AndexXa) was approved as the first and only antidote for life-threatening or uncontrolled bleeding in patients treated with rivaroxaban. Rivaroxaban was first approved by the FDA in 2011.