Benefit – Risk Peter R. Kowey, MD

1. Benefit – Risk Peter R. Kowey, MD President, Main Line Health Heart Center William Wikoff Smith Chair in Cardiovascular Research Professor of Medicine and Clinical Pharmacology Jefferson Medical College of Thomas Jefferson University

2. Unmet Medical Need • Defined efficacy/safety profile for men and women • Defined dosing/instructions for use • Simple kinetics (renal impairment/metabolism) • Durability of effect • Utility in AF of longer duration • Efficacy/safety in patients with structural heart disease

3. Tedisamil – Benefits (1) • Rapid, persistent efficacy in conversion to NSR • Dosing well defined by gender • Conversion within 30 min • Converters in sinus rhythm at 24 hrs and hospital discharge • No hemodynamic alterations • Complementary with DC cardioversion

4. Tedisamil – Benefits (2) • Effective and safe across subgroups, including high risk groups • Elderly • Women • Patients with moderate renal impairment • Patients with structural heart disease • Patients with AF of longer duration

5. Tedisamil – Potential Risks • Torsade de Pointes • Bradycardia/hypotension

6. Benefit Risk: Conclusion • Favorable benefit risk ratio • Rapid and durable conversion to NSR • Clear dose-response relationship • Low risk of TdP at recommended doses • RiskMAP facilitates appropriate use • Guidelines for patient selection and preparation • Tools for dose selection and administration • Reminders about monitoring • Observational study • Evaluate efficacy in under-represented subgroups and incidence of important adverse events