Recent ACS: STEMI, NSTEMI, UA Stabilized 1-7 Days Post-Index Event

ATLAS ACS 2: Design Recent ACS: STEMI, NSTEMI, UA Stabilized 1-7 Days Post-Index Event Exclusions: increased bleeding risk, warfarin use, ICH, prior stroke if on ASA + thienopyridine ASA 75 to 100 mg/day Stratified by Thienopyridine Use at MD Discretion Rivaroxaban 5.0 mg BID n=5,176 Rivaroxaban 2.5 mg BID n=5,174 Placebo n=5,176 PRIMARY ENDPOINTS: EFFICACY: CV Death, MI, Stroke (Ischemic, Hemorrhagic, or Uncertain Origin) SAFETY: TIMI major bleeding not associated with CABG Event driven trial with 1,002 primary efficacy events Mega et al, N Engl J Med. 2011 Nov 13

ATLAS ACS 2: Baseline Characteristics PRE HOSPITAL HOSPITAL Mega et al, N Engl J Med. 2011 Nov 13

ATLAS ACS 2: PrimairEindpunt 2 Yr KM Estimate Placebo 10.7% 8.9% HR 0.84 (0.74-0.96) mITTp = 0.008 ITT p = 0.002 ARR 1.8% NNT = 56 Geschattecumulatieveincidentie(%) Rivaroxaban (beidedoseringen) Maandennarandomisatie No. at Risk 5113 4307 3470 2664 1079 1831 421 Placebo Rivaroxaban 10229 8502 6753 5137 2084 3554 831 Mega et al, N Engl J Med. 2011 Nov 13

ATLAS ACS 2: Stent Thrombosis ARC Definite / Probable / Possible 2 Yr KM Estimate 2.9% Placebo 2.3% Estimated Cumulative Incidence (%) HR 0.69 (0.51- 0.93) mITTp = 0.016 ITT p = 0.008 Rivaroxaban (both doses) ARC Definite/probable: HR=0.65, mITT p=0.017, ITT p=0.012 Months After Randomization Mega et al, N Engl J Med. 2011 Nov 13

ATLAS ACS 2: Efficacy endpoints Dose 5.0 mg BID CV Death / MI / Stroke Cardiovascular Death Placebo 10.7% HR 0.94 mITT p=0.63 ITT p=0.57 HR 0.85 mITT p=0.028 ITT p=0.010 Placebo 4.1% 4.0% 8.8% Estimated Cumulative Incidence (%) Rivaroxaban 5 mg BID Rivaroxaban 5 mg BID NNT=53 24 24 0 0 Months Months Mega et al, N Engl J Med. 2011 Nov 13

ATLAS ACS 2: Efficacy Endpoints Very Low Dose 2.5 mg BID All Cause Death CV Death / MI / Stroke Cardiovascular Death 5% 5% HR 0.68 mITT p=0.002 ITT p=0.004 HR 0.66 mITT p=0.002 ITT p=0.005 Placebo Placebo 12% HR 0.84 mITT p=0.020 ITT p=0.007 Placebo 4.1% 10.7% 4.5% 9.1% 2.9% 2.7% Estimated Cumulative incidence (%) Rivaroxaban 2.5 mg BID Rivaroxaban 2.5 mg BID Rivaroxaban 2.5 mg BID NNT = 63 NNT = 63 NNT = 71 12 12 12 0 24 24 0 0 24 Months Months Months Mega et al, N Engl J Med. 2011 Nov 13

ATLAS ACS 2 Efficacy Endpoints Very Low Dose 2.5 mg BID Patients Treated with ASA + Thienopyridine All Cause Death CV Death / MI / Stroke Cardiovascular Death 5% 5% HR 0.85 mITT p=0.039 ITT p=0.011 Placebo Placebo HR 0.62 mITT p<0.001 ITT p<0.001 HR 0.64 mITT p<0.001 ITT p<0.001 Placebo 12% 4.5% 10.4% 4.2% 9.0% 2.7% Estimated Cumulative incidence (%) 2.5% Rivaroxaban 2.5 mg BID Rivaroxaban 2.5 mg BID Rivaroxaban 2.5 mg BID NNT = 56 NNT = 59 NNT = 71 12 12 12 0 24 24 0 0 24 Months Months Months Mega et al, N Engl J Med. 2011 Nov 13

ATLAS ACS 2: Treatment- Emergent Fatal Bleeds and ICH p=NS for Riva vs Placebo p=NS for Riva 5 vs Placebo p=NS for Riva 2.5 vs Placebo p=0.044 for Riva 2.5 vs 5 p=0.009 for Riva vs Placebo p= 0.005 Riva 5 vs Placebo P=0.037 for Riva 2.5 vs Placebo p=0.44 for Riva 2.5 vs 5 Percent (%) p=NS for all comparisons n=18 n=8 n=4 n=5 n=15 n=14 n=5 n=6 n=9 Mega et al, N Engl J Med. 2011 Nov 13

ATLAS ACS 2: Conclusion • Very low dose anticoagulation with rivaroxaban (2.5 mg BID), in addition to antiplatelet therapies, represents an effective strategy to reduce cardiovascular events in patients with a recent ACS. Mega et al, N Engl J Med. 2011 Nov 13

Recent ACS: STEMI, NSTEMI, UA Stabilized 1-7 Days Post-Index Event