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 .

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RATES OF BLEEDING 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

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

† 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

IMPORTANT SAFETY INFORMATION ( cont ’ d ) CONTRAINDICATIONS Active pathological bleeding

Severe hypersensitivity reaction to XARELTO ® ( eg , anaphylactic reactions )

WARNINGS AND PRECAUTIONS

Increased Risk of Thrombotic Events After Premature Discontinuation : Premature discontinuation of any oral anticoagulant , including XARELTO ® , in the absence of adequate alternative anticoagulation increases the risk of thrombotic events . An increased rate of stroke was observed during the transition from XARELTO ® to warfarin in clinical trials in atrial fibrillation patients . If XARELTO ® is discontinued for a reason other than pathological bleeding or completion of a course of therapy , consider coverage with another anticoagulant .