13

Results based on 15 months of data from an ongoing , 5-year postmarketing safety surveillance study to evaluate major bleeding in patients receiving XARELTO ® in a real-world clinical setting . Cases of major bleeding were identified through electronic health records from the US Department of Defense database , from January 1 , 2013 , to March 31 , 2014 .

RATES OF BLEEDING

20

COMORBID PATIENTS STUDIED

RESULTS ARE NOT INTENDED FOR DIRECT COMPARISON WITH CLINICAL TRIALS

A validated computer database algorithm developed by Cunningham et al , which identifies bleeding-related hospitalizations from a primary discharge diagnosis , was used to identify major bleeding events in this study . The definition of major bleeding is not an exact match with the ROCKET AF trial .

LIMITATIONS : This is a retrospective study and there is no comparator arm in the trial . Differences in study design , patient populations , definition of safety outcomes , and data collection methods make it difficult to make comparisons with clinical trials . 13

RATES OF BLEEDING IN ROCKET AF ( N = 7,111 ) ‡ 14

:

The event rate per 100 patient-years was 3.6 ( n = 395 ) for major bleed and 0.20 ( n = 27 ) for fatal bleed §

• 0.8 % of patients experienced an ICH ( n = 55 ) and 3.1 % of patients experienced a GI bleed ( n = 221 )

AF = atrial fibrillation ; GI = gastrointestinal ; ICH = intracranial hemorrhage . ‡XARELTO ® was evaluated versus dose-adjusted warfarin in more than 14,000 patients with

nonvalvular AF at moderate to high risk for stroke in a rigorously designed , multicenter , randomized , double-blind , double-dummy , event-driven phase III trial . XARELTO ® demonstrated effective reduction in the risk of stroke and non-CNS systemic embolism in patients with prior stroke or multiple comorbidities . 14

IMPORTANT SAFETY INFORMATION ( cont ’ d ) USE IN SPECIFIC POPULATIONS ( cont ’ d )

Labor and Delivery : Safety and effectiveness of XARELTO ® during labor and delivery have not been studied in clinical trials .

Nursing Mothers : It is not known if rivaroxaban is excreted in human milk .

§ Major bleeding from ROCKET AF study was defined as clinically overt bleeding

associated with a decrease in hemoglobin of ≥2 g / dL , transfusion of ≥2 units of packed red blood cells or whole blood , bleeding at a critical site , or with a fatal outcome . 14

Pediatric Use : Safety and effectiveness in pediatric patients have not been established .

Females of Reproductive Potential : Females of reproductive potential requiring anticoagulation should discuss pregnancy planning with their physician .