This article is more than 5 years old. Information may no longer be current.
Efficacy, safety outcomes in ROCKET AF unaffected by device malfunction
The malfunction of the whole-blood, point-of-care device used in the ROCKET AF trial did not affect efficacy and safety outcomes of the study, according to analyses published in a letter to the editor in The Journal of New England Medicine.
The original findings of ROCKET AF demonstrated that rivaroxaban (Xarelto, Janssen Pharmaceuticals) was noninferior to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation. However, an FDA recall in December 2014 of the whole-blood, point-of-care device used in the study (INRatio monitor system, Alere) called into question the accuracy of these data, according to the authors.
The recall correction notice stated that the INRatio monitor system may provide lower INR results than an automated, plasma-based laboratory INR in patients with certain specific medical conditions, including abnormal hematocrit levels, conditions associated with raised fibrinogen levels and bleeding or bruising.
Manesh R. Patel
Manesh R. Patel, MD , Anne S. Hellkamp, MS, both from the Duke Clinical Research Institute, and Keith A.A. Fox, MB, ChB, from the University of Edinburgh, on the behalf of the ROCKET AF Executive Committee and Investigators, conducted a series of post-hoc analyses of the ROCKET AF data to explore whether the malfunctioning device led to lower INR values and high doses of warfarin and bleeding.
Keith A.A. Fox
The researchers categorized trial participants based on whether they had any of the recall conditions, and then compared efficacy and safety outcomes of patients who received rivaroxaban with those who received warfarin within each of those subgroups.
According to the findings, 63% of the total safety population (n = 14,236) had no recall condition. Patients without recall conditions were younger and more likely to have a history of stroke. Patients with recall conditions were more likely to have diabetes and to have been treated with a vitamin K antagonist before the start of the trial.
The efficacy and safety outcomes in the subgroup of patients with no recall conditions were consistent with those of the overall population: noninferiority of rivaroxaban vs. warfarin for preventing stroke and systemic embolism, with similar rates of overall bleeding and lower rates of fatal and intracranial bleeding among patients treated with rivaroxaban, although higher rate of gastrointestinal bleeding, according to the authors.
The efficacy and safety outcomes for patients with any recall condition also were consistent with overall trial results. The bleeding rate was higher in both the rivaroxaban and warfarin groups, and there was a trend toward a higher RR for major bleeding with rivaroxaban than with warfarin, according to the authors.
“This finding does not support the hypothesis that device malfunction led to an increased risk of bleeding in the warfarin group of the trial,” the researchers wrote. – by Tracey Romero
Disclosure: The ROCKET AF study was supported by Johnson & Johnson Pharmaceutical Research & Development and Bayer HealthCare AG. Post-hoc analyses were supported by the Duke Clinical Research Institute. Patel reports receiving funding from AstraZeneca and Johnson & Johnson and serving on advisory boards for AstraZeneca, Bayer, Genzyme and Janssen. Fox reports receiving funding from AstraZeneca, Bayer and Jansen and honoraria from AstraZeneca, Bayer, GlaxoSmithKline, Janssen and Sanofi. Hellkamp reports no relevant financial disclosures.