1 Risk/Benefit Assessment Jeremy N. Ruskin, M.D. Director, Cardiac Arrhythmia Services Massachusetts General Hospital

2 AF Population Baseline Characteristics Parameter, no. (%) All Patients (n=773) AFFIRM Study (n=4060) Euro Heart Survey (n=3662) Male526 (68.0)2466 (60.7) 2141 (58.5) Age years (Mean ± SD)63.2 ± ± 9.0 ~ 65 Medical history CHF115 (14.9)939 (23.1) 997 (27.2) Valvular heart disease53 (6.8)198 (4.9) 766 (20.9) Coronary artery disease187 (24.2)1059 (26.1) 1161 (31.7) Cardiomyopathy194 (4.8) 328 (9.0) Hypertension402 (52.0)2063 (50.8) 2334 (63.7) Nieuwlaat R et al. Eur Heart J. 2005; 26: The AFFIRM Writing Group N Engl J Med, 2002;347:

3 Risks of Vernakalant Injection 0-24 Hours – All Patients RiskEstimate95% CL* TdP1/773 (0.13%)0.61% Hypotension † 10/773 (1.29%)2.18% Bradycardia † 13/773 (1.68%)2.66% *Based on Exact Methodology, 1-sided 95% confidence interval †SAE or discontinuation of study drug due to hypotension or bradycardia

4 Risks of Vernakalant Injection QT prolongation – moderate, transientQT prolongation – moderate, transient TdP – 1 event within 24 hours of vernakalant infusion and immediately following infusion of ibutilideTdP – 1 event within 24 hours of vernakalant infusion and immediately following infusion of ibutilide Hypotension – peri-infusional, generally transient, usually responds to saline and positioningHypotension – peri-infusional, generally transient, usually responds to saline and positioning Bradycardia – associated with cardioversionBradycardia – associated with cardioversion

5 Risks of Vernakalant Injection By History of CHF Placebo Hx CHF Vernakalant Injection Hx CHF Vernakalant Injection No Hx CHF Efficacy0% (0/16) 27% (7/26) 54% (111/205) AE hypotension * 3.7% (2/54) 14.5% (16/110) 5.3% (33/627) SBP <90 mmHg * 11.1% (6/54) 18.2% (20/110) 5.6% (35/627) *Based on events occurring within 0-24 hour time period

6 Benefits of Vernakalant Injection Patients without AF Symptoms at Min. 90 (AF >3h - ≤7d) Consistent Conversion Rates All Patients

7 Benefits of Vernakalant Injection Maintenance of sinus rhythm at 24 hours - 97%Maintenance of sinus rhythm at 24 hours - 97% Can be administered with background rate (72%) or rhythm control (20%) medicationsCan be administered with background rate (72%) or rhythm control (20%) medications Electrical cardioversion is effective in non- responders (vernakalant - 88%; placebo - 90%)Electrical cardioversion is effective in non- responders (vernakalant - 88%; placebo - 90%) Safe and effective in patients with common co-morbidities, including:Safe and effective in patients with common co-morbidities, including: –Hypertension (52% of patients in P2/3 studies) –History of ischemic heart disease (24% of patients in P2/3 studies)

8 Risk/Benefit of Vernakalant Injection Profile of ventricular arrhythmias within the first 24 hours –Ventricular Fibrillation – 2/773 (0.26%) –Torsade de Pointes (TdP) – 1/773 (0.13%) – Ventricular Tachycardia Ventricular Tachycardia Placebo N=315 Vernakalant Injection N=737 Unsustained monomorphic 30 (9.5%)58 (7.9%) Unsustained polymorphic 14 (4.4%)24 (3.3%)

9 Vernakalant Injection Risk/Benefit Summary Effective for the rapid conversion of AF to sinus rhythm with reduction of AF symptomsEffective for the rapid conversion of AF to sinus rhythm with reduction of AF symptoms An important treatment alternative for patients with acute symptomatic atrial fibrillation, including post-cardiac surgery patientsAn important treatment alternative for patients with acute symptomatic atrial fibrillation, including post-cardiac surgery patients