NOACs, including the direct thrombin inhibitor dabigatran
and the factor Xa inhibitors apixaban, edoxaban, and rivaroxaban are suitable
alternatives to VKAs for stroke prevention in AF (Table 13).
En metanalisis parecen tener menos eventos hemorragicos
aunque incluye el estudio Rocket con la polemica que ha obligado a su
reevaluacion por la FDA.
La polémica del Rocket viene porque al parecer el aparato
utilizado en el ensayo infravaloraba el INR por lo que al parecer se sobretrato
a los pacientes en el grupo warfarina.
An investigation by The
BMJ has
uncovered the use of a faulty device in a regulatory drug trial, potentially
putting patients at unnecessary risk, Deborah Cohen reports
Doctors
and scientists are calling for an independent investigation into the key trial
underpinning use of rivaroxaban to prevent ischaemic stroke in non-valvular
atrial fibrillation after The
BMJ found
that a defective point of care device was used in the warfarin arm of the
trial.
Doctors
and scientists have also told The
BMJ that
the validity of the trial—called ROCKET-AF and published in theNew
England Journal of Medicine in
20111—is
in question until such independent analysis is done.
The drug was manufactured by Bayer and marketed in the United
States by Janssen, part of Johnson and Johnson, and the companies relied on a
single trial–ROCKET-AF—to gain approval from the US and European regulators.
The trial included over 14 000 patients and found that rivaroxaban was
non-inferior to warfarin for preventing ischaemic stroke or systemic embolism.
There was no significant difference between groups in the risk of major
bleeding—although intracranial and fatal bleeding occurred less often in the
rivaroxaban group.
But
there are now concerns about these outcomes. In a letter submitted to the NEJM (as
yet unpublished) and shown to The
BMJ, former FDA cardiovascular and renal drug reviewer, Thomas
Marcinicak, says: “The care for the warfarin control arm patients [in
ROCKET-AF] appears to have been compromised.”
Earlier
last year, The
BMJ found
that the point of care device used to measure international normalised ratio
(INR) in patients taking warfarin in ROCKET-AF had been recalled in December
2014. An FDA class I recall notice (the most serious kind) said that certain
INR devices could deliver results that were “clinically significantly lower”
than a laboratory method. It added that Alere—the device …
