1. Concomitant Antiplatelet and OAC Tx: Real-World Practice In the US, ~800,000 AF patients are on concomitant OAC and antiplatelet tx 1 Patients on chronic OAC with CAD are 7x more likely to receive concomitant antiplatelet tx 2 Addition of single antiplatelet tx to OAC increases risk of major bleeding by >40% 3 Addition of double antiplatelet tx to OAC increases risk of major bleeding by ~300% 4,5 Majority of studies evaluated warfarin; novel OACs may offer theoretical benefits in concomitant antiplatelet setting 5,6 1 Douketis JD. Thromb Res. 2011;127:513-517; 2 Johnson SG. Chest. 2007;131:1500-1507; 3 Dentali F. Arch Intern Med. 2007;167:117-124; 4 Hansen ML. Arch Intern Med. 2010;170:1433-1441; 5 Dans A. Circulation. 2012 Dec 27 [ePub ahead of print]; 6 Sinnaeve PR. Circulation 2012 Dec 27 [ePub ahead of print]

2. RE-LY: Main Results Study Design: PROBE (N = 18,113) Primary Efficacy: All stroke or systemic embolismPrimary Safety: Major bleeding Mean Follow-up: 2 yearsInclusion: NVAF and ≥ 1 risk factor* Mean CHADS 2 Score: 2.1 (CHADS 2 ≥3: 33%)Mean TTR: 64% *Risk factors: prior stroke/TIA; LVEF < 40%; NYHA Class ≥ II; aged ≥ 75 years, or aged 65-74 years with DM, HTN, or CAD † for both inferiority and superiority Connolly SJ, et al. N Engl J Med. 2009;361:1139-1151 Warfarin (n=6022) Dabigatran 110 mg BID (n=6015) Dabigatran 150 mg BID (n=6076) Rate (%/y) Rate (%/y) vs warfarin Rate (%/y) vs warfarin RR (95% CI)P P Stroke/SE 1.71.530.91 (0.74–1.11).341.10.66 (0.53–0.82)<.001 † Hemorrhagic stroke 0.380.120.31 (0.17–0.56)<.0010.100.26 (0.14–0.49)<.001 Major bleeding 3.42.70.80 (0.69–0.93).0033.10.93 (0.81–1.07).31 Intracranial bleeding 0.740.230.31 (0.20–0.47)<.0010.300.40 (0.27–0.60)<.001

3. Effects of Adding Single or Dual Antiplatelet Tx on Major Bleeding in RE-LY Dans A, et al. Circulation. 2012 Dec 27 [ePub ahead of print]; Slide courtesy of Stuart J. Connolly, MD Regardless of OAC-type, addition of antiplatelet tx ↑ bleeding risk Single antiplatelet tx added to warfarin ↑ bleeding risk by 60% Adding dual antiplatelet tx to warfarin ↑ bleeding risk by 230% Dabigatran retained its benefit over warfarin in patients on antiplatelet tx

4. Recommendations for Concomitant Antiplatelet + OAC Tx with Stent Placement: The North American Perspective Stent Type Patients with AF at Moderate/High Stroke Risk (CHADS 2 ≥ 1) at: Low ST and bleeding risk High ST and low bleeding risk Any ST risk and high bleeding risk BMS Triple therapy for ≥1 month, then OAC + SAPT for 12 months Triple therapy for ≥6 months, then OAC + SAPT for 12 months Triple therapy for ≥1 month, then OAC + SAPT for 12 months DES Triple therapy for ≥6 months, then OAC + SAPT for 12 months Triple therapy for 12 months Not recommended After 12 months, OAC should be resumed indefinitely. (In patients at high risk for atherothrombotic events, including ST, continued SAPT with OAC should be considered after 12 months) BMS, bare-metal stent; DES, drug-eluting stent; OAC, oral anticoagulant (warfarin); SAPT, single antiplatelet therapy (aspirin or clopidogrel); ST, stent thrombosis; triple therapy (warfarin, aspirin, and clopidogrel) Faxon DP. Circ Cardiovasc Interv. 2011;4:522-534

5. Concomitant Antiplatelet and OAC Tx: Pearls for Practice Tx decisions require careful balance of benefits vs inherent risks Keep concomitant durations as short as possible –Use bare-metal stents, when possible Lessen intensity of anticoagulation. –Target tighter INR for warfarin (target INR 2.0-2.5) –Lower doses of novel OACs –Lower doses of antiplatelet(s) Consider prophylactic use of proton-pump inhibitors to reduce GI bleeding Avoid concomitant NSAID use Faxon DP. Circ Cardiovasc Interv. 2011;4:522-534