FDA Approves Rivaroxaban for Stroke Prevention in AF

The FDA has approved rivaroxaban (Xarelto, Johnson & Johnson) for stroke reduction in people with non-valvular atrial fibrillation. The label will include a boxed warning that people should not discontinue taking the drug without talking with a healthcare professional. The FDA will also require that patients getting the drug receive a Medication Guide describing the risks and adverse reactions associated with the drug.

The label does not provide firm guidance on the relative merits of rivaroxaban and warfarin in AF patients:

There are limited data on the relative effectiveness of XARELTO and warfarin in reducing the risk of stroke and systemic embolism when warfarin therapy is well-controlled.

Some panelists at the FDA advisory panel in September had suggested that rivaroxaban should only be used in patients unable to take warfarin.

In a story in the Wall Street Journal, Tom Burton notes that in approving rivaroxaban for this indication the FDA overruled its own staff recommendation to issue a complete response letter to J&J’s NDA.

Click here to download a PDF of the Xarelto label.

Click here for previous CardioBrief coverage of rivaroxaban.

Here is the FDA press release:

FDA approves Xarelto to prevent stroke in people with common type of abnormal heart rhythm

The U.S. Food and Drug Administration today approved the anti-clotting drug Xarelto (rivaroxaban) to reduce the risk of stroke in people who have abnormal heart rhythm (non-valvular atrial fibrillation).

Atrial fibrillation occurs in more than 2 million Americans and is one of the most common types of abnormal heart rhythm. In atrial fibrillation, the beating of the heart’s two upper heart chambers (atria) is irregular and poorly coordinated. This leads to blood pooling in these chambers, resulting in blood clots. Non-valvular atrial fibrillation refers to atrial fibrillation in patients who do not have significant problems in their heart valves.

“Atrial fibrillation can lead to the formation of blood clots, which can travel to the brain, blocking blood flow and causing a disabling stroke,” said Norman Stockbridge, M.D., Ph.D., director of the Division of Cardiovascular and Renal Products in the FDA’s Center for Drug Evaluation and Research. “This approval gives doctors and patients another treatment option for a condition that must be managed carefully.”

A stroke occurs if the flow of blood to a portion of the brain is blocked. If brain cells die or are damaged because of a stroke, symptoms occur in the parts of the body that these brain cells control. Stroke symptoms include sudden weakness; paralysis or numbness of the face, arms, or legs; trouble speaking or understanding speech; and trouble seeing.
The safety and efficacy of Xarelto were evaluated in a clinical trial with more than 14,000 patients comparing Xarelto with the anti-clotting drug warfarin. In the trial, Xarelto was similar to warfarin in its ability to prevent stroke.
For people taking the drug for atrial fibrillation, Xarelto should be taken one time a day with the evening meal so that it will be completely absorbed.

As with other anti-clotting drugs, Xarelto can cause bleeding that, rarely, can lead to death. Bleeding was the most common adverse event reported by patients treated with Xarelto in the major clinical trial for the prevention of stroke in non-valvular atrial fibrillation. In that trial, Xarelto’s risk of major bleeding was similar to that of warfarin; however, it caused less bleeding into the brain and more bleeding into the stomach and intestines.

Xarelto has a boxed warning to make clear that people using the drug should not discontinue it before talking with their health care professional. Discontinuing the drug can increase the risk of stroke.

An FDA-required Medication Guide, which will be given to patients and caregivers when Xarelto is dispensed, describes the risks and adverse reactions people should be mindful of when using the drug.

Xarelto is marketed in the United States by Titusville, N.J.- based Janssen Pharmaceuticals Inc.

On July 1, 2011, the FDA approved Xarelto to reduce the risk of blood clots, deep vein thrombosis, and pulmonary embolism following knee or hip replacement surgery.

For information:

FDA: Approved Drugs: Questions and Answers

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Here is the press release from Johnson & Johnson:

FDA Approves XARELTO® (rivaroxaban)
to Reduce the Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation

XARELTO® Combines Proven Effectiveness and Demonstrated Safety Profile
with Convenient, Once-Daily Dosing


RARITAN, NJ, November 4, 2011 – Janssen Pharmaceuticals, Inc. announced today the U.S. Food and Drug Administration (FDA) has approved XARELTO® to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. XARELTO® is the only oral anticoagulant approved in the U.S. that offers once-daily dosing, without the need for routine blood monitoring.

“Today’s approval of XARELTO® offers physicians a new option to reduce stroke risk in patients who are living with atrial fibrillation, and the continuous threat of strokes,” said Gerald V. Naccarelli*, M.D., Professor of Medicine, Chief of Division of Cardiology, Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center. “A majority of my atrial fibrillation patients are on multiple medicines for conditions that further increase the risk of stroke. I welcome a therapy like XARELTO® that has demonstrated effectiveness and safety in these patients, with the added convenience of a once-daily dose.”

XARELTO® is approved to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation at a dose of 20 mg once daily, or 15 mg once daily for patients with moderate to severe renal impairment, taken with the evening meal. There are limited data on the relative effectiveness of XARELTO® and warfarin in reducing the risk of stroke and systemic embolism when warfarin therapy is well-controlled.

Atrial fibrillation (AFib) is the most common cardiac rhythm disorder1 and affects more than 2.2 million people in the U.S.2 In patients with AFib, the heart’s irregular heartbeat makes them vulnerable to the formation of a blood clot in the atria, which sometimes can break off and travel to the brain, potentially resulting in a stroke.3 The presence of common conditions such as high blood pressure, heart failure, diabetes, and prior stroke, along with being over the age of 75, are factors that further increase the risk of stroke in people living with AFib. People living with AFib are at a five-fold increased risk for stroke compared with the general population.


“The prevalence of atrial fibrillation is increasing, and many patients who are at risk for stroke are not currently being managed effectively or optimally,” said Robert M. Califf*, M.D., ROCKET AF study co-chairman and Vice Chancellor for Clinical Research at Duke University. “In clinical studies, XARELTO® was shown to be effective in patients who are at increased risk of stroke, and especially in those with co-morbidities such as high blood pressure or diabetes, and other factors that increase the risk of stroke. These patients represent many of those with the most to gain from effective anticoagulation.”

The approval of XARELTO® in this indication was based on the pivotal, double-blind Phase 3 ROCKET AF (RivaroxabanOnce-daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for the prevention of stroke andEmbolism Trial in Atrial Fibrillation) global clinical trial, in which once-daily rivaroxaban effectively reduced the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, with major bleeding rates comparable to warfarin. In bleeding categories of great concern, such as bleeding into a critical organ and fatal bleeding, fewer events were observed with rivaroxaban. In the categories of bleeding resulting in transfusions and gastrointestinal bleed, more events were observed with rivaroxaban. To see the details of the ROCKET AF trial published in the New England Journal of Medicine, please click here.

“Today’s FDA approval of XARELTO® gives patients with nonvalvular atrial fibrillation a new anticoagulation option – one that helps reduce the risk of stroke and has proven tolerability and convenient once-daily dosing and administration,” said Peter M. DiBattiste, M.D., Global Therapeutic Area Head, Cardiovascular and Metabolism, Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD). “We are pleased to bring to market a medicine that will potentially help millions of patients.”

Janssen Pharmaceuticals, Inc. holds U.S. marketing rights for XARELTO®, and will be supported by the Bayer HealthCare U.S. sales force in designated hospital accounts.

FDA has required a Risk Evaluation and Mitigation Strategy (REMS) for XARELTO® to communicate the risks of increased risk of thrombotic events, including stroke, if XARELTO® is discontinued without introducing an adequate alternative anticoagulant in patients with nonvalvular atrial fibrillation, and the potential decreased efficacy of XARELTO® (15 mg and 20 mg) if not taken with the evening meal. The XARELTO® REMS consists of a Medication Guide and a communication plan.


In addition to this new indication, XARELTO® is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in people undergoing knee or hip replacement surgery. XARELTO®has been used by more than a million patients worldwide in the orthopedic setting. XARELTO® belongs to a group of medicines called anticoagulants. It works by blocking the blood clotting Factor Xa and thereby reduces the tendency of the blood to form clots.

XARELTO® is the fifth New Drug Application the U.S. FDA has approved from the Janssen Pharmaceutical Companies this year.

J&JPRD (the research and development affiliate of Janssen) and Bayer HealthCare are developing rivaroxaban jointly. The companies are evaluating rivaroxaban for a broad range of disorders in which blood clotting plays a major role. The extensive program of clinical trials makes rivaroxaban the most studied oral, Factor Xa inhibitor in the world today. By the time of its completion, more than 75,000 patients will have participated in the rivaroxaban clinical development program.


  1. William R. Muscatello says

    How do I get a copy of this report to show my doctor?

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