1. How Much AF is Too Much AF? Do I Initiate Anticoagulation Based on AF Detected on Device Monitoring? Kenneth W. Mahaffey, MD, FACC Professor of Medicine, Cardiology Faculty Associate Director, DCRI Director, DCRI MegaTrials & CEC Duke Clinical Research Institute Durham, NC

2. Disclosures Consultant Fees/Honoraria Adolor; Amgen; AstraZeneca; Bayer HealthCare; Biotronik, Inc.; Boehringer Ingelheim; Bristol-Myers Squibb; Daiichi Sankyo, Inc.; Eli Lilly; Elsevier; Exeter Group; Forest; Genentech; Gilead; GlaxoSmithKline; Haemonetics; Johnson and Johnson; Medtronic; Merck and Co., Inc.; Novartis; Orexigen Therapeutics; Ortho-McNeil; Pfizer Inc; sanofi-aventis U.S. Inc.; Sun Pharma; Springer Publishing; WebMD Research/Research Grants Abbott Vascular; Amgen; Amylin; AstraZeneca; Baxter; Bayer HealthCare; Boehringer Ingelheim; Bristol-Myers Squibb; Cordis; Daiichi Sankyo, Inc.; Edwards Lifesciences; Eli Lilly; GlaxoSmithKline; Guidant; Ikaria; INC Research; Johnson and Johnson; Kai Pharmaceuticals; Luitpold; Merck and Co., Inc.; Portola Pharmaceuticals; Pozen; Regado Biosciences; Roche; sanofi-aventis U.S. Inc.; Schering Plough; The Medicines Company

3. Screening for AF: Key Issues Predicting AF Screening Finding Quantifying Determining risk Treating Modifying outcomes

4. ASSERT Trial Stroke or Systemic Embolism Healy JS, et al. N Engl J Med. 2012;366:120-129. Device-Detected Atrial Tachyarrhythmia Detected 0-3 months No Asymptomatic Atrial Tachycardia Detected 0-3 months HR = 2.49 95% CI, 1.28-4.85 P = 0.007 # at RiskYear 0.51.01.52.02.5 + 261249238218178122 - 2,3192,1452,0701,9221,556 1,197 Years of Follow-up T 0 at 3-month visit Cumulative Hazard Rates 00.51.01.52.0 2.5 0.0 0.02 0.04 0.06 0.08 0.10

5. TRENDS Trial AF Burden & Thromboembolic Events Annualized Rate (Stroke & TIA) Annualized Rate (Stroke only) Zero burden1.1%0.5% Low burden < 5.5 hours 1.1% High burden ≥ 5.5 hours 2.4%1.8% Glotzer TV, et al. Circ Arrhythm Electrophysiol. 2009;474-480.

6. IMPACT Trial Device Monitoring Guided Anticoagulation Ip J, et al. Am Heart J. 2009;158:364-370. Patient Population: ─N = 2,718 ─Dual-chamber ICD or CRT-D device ─CHADS 2 ≥ 1 Primary endpoint = composite of stroke, systemic embolism and major bleeding Hypothesis: ─Initiation and withdrawal of anticoagulant therapy guided by ambulatory monitoring will improve clinical outcomes Phase A (N = 227) completed 2009 Phase B ongoing 6m12m 18m 24m 30m 36m Randomize 1:1 Group 2 (Control) Group 1 (Intervention) Conventional follow-up + physician-directed anticoagulation Conventional follow-up + HM-guided anticoagulation

7. Summary Type of AF or AF burden should not influence stroke prevention treatment strategy Antithrombotic therapy for patients with AF should be guided by risk stratification based on validated prediction tools Patients with history of AF in sinus rhythm are not necessarily low risk