December 8th, 2010
ROCKET-AF: Stroke Prevention and Beyond!
Manesh R. Patel, MD
The ROCKET-AF trial, which was recently presented at AHA, showed that the experimental factor Xa inhibitor rivaroxaban was as effective as warfarin in preventing stroke in 14,264 AF patients and did not increase their risk of bleeding. CardioExchange welcomes one of the trial’s investigators, Manesh Patel of the Duke Clinical Research Institute, to answer our questions about ROCKET-AF.
Q: Not surprisingly, ROCKET-AF has generated a lot of interest both at AHA and beyond. It seems the effects in the rivaroxaban arm of the trial were similar compared to those seen in the warfarin arm, regardless of patients’ time in therapeutic INR range during the trial. What about patients who were previously stable on warfarin, which is a subgroup that did not seem to benefit from dabigatran?
A: The effects of rivaroxaban were similar in both patients who were previously treated with vitamin K anatagonists (VKAs) and those who were naive to VKAs.
Q: Were the effects similar across all ranges of CHADS scores, with respect to trends and/or interaction terms?
A: As described, the mean CHADs score was 3.5. The treatment effect was qualitatively consistent across all ranges of CHADS scores (2-6) with larger confidence intervals for the groups with smaller number of patients. There was no statistical interaction for effect across the CHADS scores.
Q: With respect to the superiority analysis, was this prespecified to be modified or non-modified intention to treat?
A: As stated, once noninferiority was established, the superiority analysis was prespecified to be analyzed first in patients who took at least one dose of the study drug with events while on treatment, and then by intention-to-treat principle.
Q: Given these data on rivaroxaban, now adding to the available data on dabigatran in a lower-risk sample, is there anybody whom you think should remain on warfarin as opposed to being on either of these two new agents?
A: There may be patients who have been stable on warfarin for years that may not need to be changed. However, for AF patients going on to therapy there are now good alternatives.
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What about its safety profile regarding pregnancy?
Competing interests pertaining specifically to this post, comment, or both:
None
Intention to treat analysis is generally regarded as the most valid method when assessing superiority in a trial, and may more accurately reflect what might occur in practice outside of a clinical trial. Why was the decision to run a per protocol superiority analysis made, and how does this affect the statistical validity of the trial?
Competing interests pertaining specifically to this post, comment, or both:
none
Analysis are under way to provide the full results. In this A fib population and the patients at risk for pregnancy is quite low (median age 73).
The primary hypothesis of this study was non-inferiority and this was tested in the per-protocol population to reduce bias (patient’s not on study drug are more likely to be non-inferior to warfarin)
Once non-inferiority was established the superiority was tested in patients on treatment and then by intention to treat – understanding this represents patients on and off therapy with all follow up in this long term trial.