ROCKET AF Rivaroxaban meets primary end

point

The First oral Xa is non-Inferior toWarfarin in AF

Background

• Rivaroxaban (BAY 59-7939) is an oral anticoagulant invented and manufactured by Bayer; in a number of countries it is marketed as Xarelto.

• 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 possible.

• Rivaroxaban is an oxazolidinone derivative optimized for inhibiting both free Factor Xa and Factor Xa bound in the prothrombinase complex.

• 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 stroke.

Results

• 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).

CME questions

• 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 Dabigatran

• Is • 1- 150 & 75• 2-150 & 110• 3-not yet approved by FDA

• 1- 150 & 75