Rivaroxaban meets primary end
The First oral Xa is non-Inferior to
Warfarin in AF
• Rivaroxaban (BAY 59-7939) is an oral
anticoagulant invented and manufactured by
Bayer; in a number of countries it is marketed
• It is the first available orally active
direct factor Xa inhibitor.
• Rivaroxaban is well absorbed from the gut
and maximum inhibition of factor Xa occurs
four hours after a dose. The effects lasts 8–12
hours, but factor Xa activity does not return to
normal within 24 hours so once-daily dosing is
• Rivaroxaban is an oxazolidinone derivative
optimized for inhibiting both free Factor Xa
and Factor Xa bound in the
• It is a highly selective
direct Factor Xa inhibitor with oral
bioavailability and rapid onset of action.
• Inhibition of Factor Xa interrupts the intrinsic
and extrinsic pathway of the
blood coagulation cascade, inhibiting
both thrombin formation and development of
thrombi. Rivaroxaban does not inhibit
thrombin (activated Factor II), and no effects
on platelets have been demonstrated.
• ROCKET AF is double-blind phase 3 study in
more than 14 000 patients with nonvalvular
atrial fibrillation (AF).
• They were randomized to 20-mg rivaroxaban
once daily (or 15 mg in patients with
moderate renal impairment at screening) or
to dose-adjusted warfarin (titrated to an
international normalized ratio [INR] of 2.5).
• The study was led by the Duke Clinical
Research Institute, Durham, NC, and an
international academic executive committee.
Higher Risky AF
• It has recently been reported that the patients
enrolled in ROCKET-AF are at higher risk of
stroke than those who have participated in
other similar trials, with 90% having a
CHADS2 score of 3 or higher compared with
fewer than 50% of those enrolled in four
comparable studies: RE-LY, ACTIVE
W,AMADEUS, and SPORTIF V.
• CHADS2 is a tool used by doctors to assess
stroke risk and subsequent need for
anticoagulation therapy in patients with AF;
the higher the score, the greater the risk of
• Non Inferiority was met with regard to all-
cause stroke and non-central nervous system
systemic embolism .
• The rates of the composite of major and
nonmajor clinically relevant bleeding were
comparable (the primary safety end point).
• In Re-Ly trial , risk of hemorrhagic stoke with
warfarin compared to Dabigatran 150 mg po
Twice daily was
• 1- two folds
• 2-no difference
• 3-three folds but not statistically significant.
• 4-Four fold but statistically significant .
• 4-Four fold but statistically significant
• In the RE-LY trial, the rate of hemorrhagic stroke
was 0.38% per year in the warfarin group,
compared with 0.12% per year with 110 mg of
dabigatran (P < .001) and 0.10% per year with
150 mg of dabigatran (P < .001). These data
revealed that warfarin had an almost 3-fold
increase in hemorrhagic stroke compared with
dabigatran 110 mg and an almost 4-fold increase
in hemorrhagic stroke compared with dabigatran
150 mg. Both attained statistical significance.
• The doses in mg approved by FDA for
• 1- 150 & 75
• 2-150 & 110
• 3-not yet approved by FDA