U.S. Food and Drug Administration reviewers have warned against immediate approval of rivaroxaban (Xarelto) and questioned effectiveness of the medication for preventing stroke in high-risk atrial fibrillation patients.
Warfarin is the standard for preventing stroke in patients with atrial fibrillation, a common heart arrhythmia. In order to gain approval, drug maker Johnson & Johnson needed to prove the proposed drug is as effective as older treatment warfarin.
Rivaroxaban already is approved in the United States as an anti-clotting agent after knee and hip surgery.
The company’s large-scale Phase 3 ROCKET trial has not convinced FDA reviews, who in a briefing document said the trial comparing rivaroxaban and warfarin was ” not adequate to determine whether rivaroxaban is as effective for its proposed indication in comparison to warfarin when the latter is used skillfully.”
Last year’s ROCKET AF trial was a double blind study that enrolled 14,264 high-risk atrial fibrillation patients. More than half had previously had a stroke, transient ischemic attack or an embolism.
Investigators found that as compared to warfarin, rivaroxaban decreased the rate of stroke and non-central nervous system embolism, but was not found to be superior in preventing blood clots and strokes.
FDA reviewers said there remained “a lack of substantial evidence that rivaroxaban will have its desired effect when used as recommended in labeling,” noting that even if the drug gets the green light it should be used as a third option behind other treatments, which include warfarin and newly-approved drug pradaxa.
Warfarin has low patient compliance rates because patients must get regular blood test monitoring because it can be difficult to get the dosing just right. It also can have reactions with certain foods and other medications.
Additional concerns voiced included the risk of bleeding and a higher risk of stroke seen when patients stop taking the drug. FDA officials will make a final decision on rivaroxaban on Thursday at a meeting of the Cardiovascular and Renal Drugs Advisory Committee.
In the United States, over 850,000 people are hospitalized from an arrythmia, a general term for a large group of conditions that results from abnormal electrical activity in the heart. Also known as cardiac dysrhythmias, they can cause the heart to beat too fast, too slow, or in an irregular pattern.
The conditions can range from benign to life-threatening, and in some cases can cause sudden death. Common ‘palpitations’, such as premature ventricular contractions, may be simply uncomfortable and not need treatment, but others like atrial fibrillation need treatment because they increase the risk of stroke. In many cases, arrythmias will need treatment because they can lower blood pressure to the point that a patient can faint.