# Presentation: 737656

## Risk/Benefit Assessment

**Jeremy N. Ruskin, M.D.**
*Director, Cardiac Arrhythmia Services*
*Massachusetts General Hospital*

## AF PopulationBaseline Characteristics

| Parameter, no. (%) | All Patients
(n=773) | AFFIRM Study
(n=4060) | Euro Heart Survey
(n=3662) |
| --- | --- | --- | --- |
| Male | 526 (68.0) | 2466 (60.7) | 2141 (58.5) |
| Age years (Mean ± SD) | 63.2 ± 13.2 | 69.7 ± 9.0 | ~ 65 |
| Medical history |  |  |  |
| CHF | 115 (14.9) | 939 (23.1) | 997 (27.2) |
| Valvular heart disease | 53 (6.8) | 198 (4.9) | 766 (20.9) |
| Coronary artery disease | 187 (24.2) | 1059 (26.1) | 1161 (31.7) |
| Cardiomyopathy |  | 194 (4.8) | 328 (9.0) |
| Hypertension | 402 (52.0) | 2063 (50.8) | 2334 (63.7) |

**Nieuwlaat R et al. Eur Heart J. 2005; 26:2422-34**
**The AFFIRM Writing Group N Engl J Med, 2002;347:1825-33**

## Risks of Vernakalant Injection0-24 Hours – All Patients

| Risk | Estimate | 95% CL* |
| --- | --- | --- |
| TdP | 1/773 (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**

## Risks of Vernakalant Injection

**QT prolongation – moderate, transient**
**TdP – 1 event within 24 hours of vernakalant infusion and immediately following infusion of ibutilide**
**Hypotension – peri-infusional, generally transient, usually responds to saline and positioning **
**Bradycardia – associated with cardioversion**

## Risks of Vernakalant Injection By History of CHF

|  | Placebo
Hx CHF | Vernakalant Injection
Hx CHF | Vernakalant Injection 
No Hx CHF |
| --- | --- | --- | --- |
| Efficacy | 0%
(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**

## Benefits of Vernakalant Injection

**Patients without****AF Symptoms**
*at Min. 90 (AF >3h - ≤7d)*

**Consistent Conversion Rates**
*All Patients*

## Benefits of Vernakalant Injection

**Maintenance of sinus rhythm at 24 hours - 97% **
**Can be administered with background rate (72%) or rhythm control (20%) medications**
**Electrical cardioversion is effective in non-responders (vernakalant - 88%; placebo - 90%) **
**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)**

## 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%) |

## Vernakalant Injection Risk/Benefit Summary

**Effective 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 patients**