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Thursday, December 03, 2015

Was the clinical trial that lead to the approval of Rivaroxaban for A Fib flawed?

The Rocket -AF trial was key in obtaining FDA approval for rivaroxaban, ( Xarelto) in part because of the decrease bleeding  in the riva group versus the warfarin group, at least in terms of fatal and intracranial bleeding. It was shown to be non-inferior in regard to stroke prevention.However, questions have been raised about the devices used  to measure to monitor warfarin therapy. It has been alleged that the instruments had a tendency to give falsely low values for the INR. If so , one wonders if the physicians  whoever monitored it would then increase the warfarin dose   to reach the target INR and that might account for the higher bleeding rates in the warfarin group or a relatively lower rate in the rivaroxaban group.

 The warfarin control arms of these trials can be problematic.There is always the issue of what percentage of time were the patients in the target INR range.Further ,heaven forbid, there may be even opportunities  for stacking the deck.

There is still more drama to the story -the FDA panel that reviewed the data did not recommend its approval but the full deciding body at the FDA voted in favor. Some has also expressed concern about the current leading candidate  for the head of the FDA since he was a prominent investigator in the trial.

We may never know  or if we do it may take a while to sort that out, Meanwhile what about all the folks taking Xarelto? Can they be confident that this new or novel anticoagulant affords them greater safety than  warfarin?Should they consider switching to apixaban? Should they even worry , after all there have been other trials that demonstrated efficacy and safety in the setting of venous thromboembolism and for prophylaxis in hip replacement.

More details can be found at Larry Huston;s excellent site  "Cardiobrief". He also raises the issue of possible COI with the candidate for the Head Of the FRA, Robert M Califf who was a principal investigator in the Rocket-Af trial. As usual Dr Roy Poses offers important insights into the issue of COI and the  ever spinning revolving door in health care in regard to the Dr. Califf and the unprecedented endorsement  of him for the FDA post by the editorial folks at the NEJM.See here.

 12/13/15Addendum; The folks who did the Rocket-af say they have now checked into the matter and that there is no need to worry. Sort of a move along nothing to see here type statement.  Unfortunately  they have not yet made public the data they collected and used to reach that reassuring conclusion. Stay tune.See here for details  from the blog Cardiobrief by Larry Hustin which as usual has a wealth of useful information from the world of cardiology.

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