Rivaroxaban Trial Threatened by Possibly Flawed INR Measurements

By Joe Elia

Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM

A faulty device used in the trial leading to approval of rivaroxaban — a direct-acting oral anticoagulant — has called those results into question, according to an investigation reported in The BMJ. The trial's authors, however, refute the concern.

The ROCKET AF trial investigators distributed the point-of-care device to measure international normalized ratios after dosing with warfarin, the comparator drug. However, the instrument was later recalled by the FDA; it was distributed to all 1200 participating sites according to the study's protocol. The device was prone to giving falsely low INR readings.

Such readings would have prompted higher doses of warfarin — resulting in higher bleeding risks for the drug — making rivaroxaban seem comparatively safer.

In a letter to the New England Journal of Medicine, where the ROCKET AF results appeared in 2011, the trial's authors present a reanalysis of their data and conclude that use of the device "did not have any significant clinical effect on the primary efficacy and safety outcomes in the trial."

Asked to comment, NEJM Journal Watch Cardiology Editor-in-Chief Harlan Krumholz said, "If the trial data were publicly available — especially that pertaining to INR testing — it would reduce uncertainty about the trial and allow more informed choice in the use of rivaroxaban."