Big Questions with Xarelto Study

The purpose of this post is to introduce my most recent column over at theHeart.org | Medscape Cardiology in which I address recent concerns about the drug rivaroxaban (Xarelto).

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In 2014, Rivaroxaban (Xarelto) was the most prescribed new oral anticoagulant (NOAC). Millions of patients have atrial fibrillation, so it’s fair to call it a blockbuster drug.

Recently, however, concerns have arisen about the validity of the results of the pivotal trial, called ROCKET-AF, that led to FDA approval. Recall that in the 14,000-patient-strong multicenter ROCKET-AF trial, rivaroxaban was found to be noninferior to warfarin for stroke prevention in patients with AF. Major bleeding rates were similar.

The new concern is that the device used to test INR levels (International Normalized Ratio levels are used to adjust warfarin dosing) in patients in the warfarin arm of ROCKET-AF is now under a Class I FDA recall. The device can give falsely now INRs in certain conditions.

This is huge because the key to a clinical trial is making sure two drugs are compared fairly. If warfarin-treated patients were managed with a faulty device, that could skew the results toward rivaroxaban.

In fact, concerns about the robustness of the warfarin arm of ROCKET-AF are not new. At the time of FDA approval, some experts cited the less than skillful use of warfarin in the trial as a reason to doubt the relative efficacy and safety of rivaroxaban.

Writing in the British Medical Journal, Deborah Cohen, an associate editor at the BMJ, makes the case that these revelations cast significant doubt on the validity of the ROCKET-AF trial. She and other experts call for independent verification of the study’s results. (You can read the letter for free; it’s written in plain language, which is striking in its effect.)

To counter these concerns, the ROCKET-AF investigators (from the Duke Clinical Research Institute) went back to their data-sheets to test whether the recalled INR device affected the results. They found that it did not. Their analysis, which was published in the New England Journal of Medicine, upheld the main results of the trial: rivaroxaban remained noninferior to warfarin for stroke prevention without an increase in major bleeding.

I have used rivaroxaban since its approval in 2011. During these years, other studies and observations have informed our experience with this drug. These studies, and my personal experience with rivaroxaban, have been positive.

In my most recent column over at theHeart.org on Medscape, I explain the concerns with ROCKET-AF, list four reasons to remain confident about rivaroxaban, and send a message to the Bayer corporation, the makers of rivaroxaban and keepers of the ROCKET-AF data.

The title of the post is: Rivaroxaban: It’s Not Time to Cut the Rope, Yet

JMM