1. Patients Are Undertreated NABOR Warfarin/Warfarin + Aspirin No Treatment Patients, % Waldo AL, et al. J Am Coll Cardiol. 2005;46:1729-1736. [3] Retrospective cohort study of inpatients at 21 teaching, 13 community, and 4 Veterans Affairs hospitals in the United States

2. Patients Are Undertreated Meta-analysis Ogilvie IM, et al. Am J Med. 2010;123:638-645. [5] Patients with prior stroke/transient ischemic attack –25 of 29 studies reported undertreatment –21 of 29 studies reporting oral anticoagulant use < 60% Patients with CHADS 2 ≥ 2 –7 of 9 studies reporting treatment < 70%

3. AVERROES: Apixaban vs Aspirin Primary Outcome Connolly SJ, et al. N Engl J Med. 2011;364:806-817. [7] Outcome ApixabanAspirinApixaban vs Aspirin Annual Rate Hazard Ratio (95% Confidence Interval)P Value Stroke or systemic embolism 1.63.70.45 (0.32-0.62)<.001 Stroke1.63.40.46 (0.33-0.65)<.001 –Ischemic1.13.00.37 (0.25-0.55)<.001 –Hemorrhagic0.20.30.67 (0.24-1.88).45 –Disabling or fatal1.02.30.43 (0.28-0.65)<.001 Systemic embolism0.10.40.15 (0.03-0.68).01

4. New Oral Anticoagulants Stroke or System Embolic Event (vs Warfarin) a. Connolly SJ, et al. N Engl J Med. 2009;361:1139-1151 [7] ; b. Patel MR, et al. N Engl J Med. 2011;365:883-891 [9] ; c. Granger CB, et al. N Engl J Med. 2011;365:981-992 [10] ; d. Giugliano RP, et al. N Engl J Med 2013;369:2093-2104. [11] Risk Ratio (95% Confidence Interval)P Value RE-LY a Dabigatran 150 mg 0.66 (0.53-0.82)<.001 ROCKET AF b Rivaroxaban 0.88 (0.75-1.03).12 ARISTOTLE c Apixaban 0.79 (0.66-0.95).01 ENGAGE AF-TIMI 48 d Edoxaban 60 mg 0.87 (0.73-1.04).08

5. a. Connolly SJ, et al. N Engl J Med. 2009;361:1139-1151 [7] ; b. Patel MR, et al. N Engl J Med. 2011;365:883-891 [9] ; c. Granger CB, et al. N Engl J Med. 2011;365:981-992 [10] ; d. Giugliano RP, et al. N Engl J Med 2013;369:2093-2104 [11] ; e. Ruff CT, et al. Lancet. 2014;383:955-962. [8] New Oral Anticoagulants (cont) Stroke or Systemic Embolic Event (vs Warfarin) Risk Ratio (95% Confidence Interval)P Value RE-LY a Dabigatran 150 mg 0.66 (0.53-0.82)<.001 ROCKET AF b Rivaroxaban 0.88 (0.75-1.03).12 ARISTOTLE c Apixaban 0.79 (0.66-0.95).01 ENGAGE AF-TIMI 48 d Edoxaban 60 mg 0.87 (0.73-1.04).08 Combined (Random) e 0.81 (0.73-0.91)<.0001 Intracranial hemorrhage (Combined) e 0.48 (0.39-0.59)<.0001

6. Some Foods High in Vitamin K NIH website. [12] Kale Spinach Brussels sprouts Turnip greens Lettuce Broccoli Endive Parsley Swiss chard Mustard greens Collards

7. New oral anticoagulants reduced the risk for intracranial hemorrhage compared with warfarin New oral anticoagulants have minimal food and drug interactions Long-term adherence to this treatment is absolutely necessary Clinicians should develop patient education strategies New oral anticoagulants do not require monitoring Summary

8. Abbreviations ACE = angiotensin-converting enzyme AF = atrial fibrillation ARISTOTLE = Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation AVERROES = Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients who have Failed or are Unsuitable for Vitamin K Antagonist Treatment CAD = coronary artery disease CHA 2 DS 2 -VASc = congestive heart failure (or left ventricular systolic dysfunction), hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65 to 74 years, and sex category (ie, female sex) ENGAGE AF-TIMI 48 = Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation— Thrombolysis in Myocardial Infarction 48 INR = international normalized ratio NABOR = National Anticoagulation Benchmark and Outcomes Report RE-LY = Randomized Evaluation of Long-Term Anticoagulant Therapy ROCKET AF = Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation

9. References 1. Hohnloser SH, Duray GZ, Baber U, Halperin JL. Prevention of stroke in patients with atrial fibrillation: current strategies and future directions. Eur Heart J Suppl. 2008(Suppl H):H4-H10. 2. Granger CB. Newer oral anticoagulants should be used as first-line agents to prevent thromboembolism in patients with atrial fibrillation and risk factors for stroke or thromboembolism. Circulation. 2012;125:159- 164. 3. Waldo AL, Becker RC, Tapson VF, Colgan KJ. Hospitalized patients with atrial fibrillation and a high risk of stroke are not being provided with adequate anticoagulation. J Am Coll Cardiol. 2005;46:1729-1736. 4. Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation. 2007;115:2689-2696. 5. Ogilvie IM, Newton N, Welner SA, Cowell W, Lip GYH. Underuse of oral anticoagulants in atrial fibrillation: A systematic review. Am J Med. 2010;123:638-645.

10. References (cont) 6. Warfarin drug interactions. http://www.drugs.com/drug-interactions/warfarin.html. Accessed November 5, 2014. 7. Connolly SJ, Ezekowitz MD, Yusuf S, et al; and the RE-LY Steering committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-1151. 8. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomized trials. Lancet. 2014;383:955-962. 9. Patel MR, Mahaffey KW, Garg J, et al; for the ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365;883-891. 10. Granger CB, Alexander JH, McMurray JJV, et al; for the ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-992.

11. References (cont) 11. Giugliano RP, Ruff CT, Braunwald E, et al; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013;369:2093-2104. 12. National Institutes of Health. Important information to know when you are taking Coumadin® and Vitamin K. http://ods.od.nih.gov/pubs/factsheets/coumadin1.pdf. Accessed November 5, 2014. 13. Wanek MR, Horn ET, Elapavaluru S, Baroody SC, Sokos G. Safe use of hemodialysis for dabigatran removal before cardiac surgery. Ann Pharmacotherapy. 2012;46:e21.