Abstract and Introduction
Abstract
Purpose. The pharmacology, pharmacokinetics, safety, clinical efficacy, and role of intravenous vernakalant hydrochloride for the rapid conversion of atrial fibrillation (AF) to normal sinus rhythm are reviewed.
Summary. Vernakalant, currently being evaluated by the Food and Drug Administration (FDA), for the termination of atrial fibrillation, differs in pharmacology from other antiarrhythmics; it achieves action potential interference through blockade of sodium and potassium currents. Vernakalant's actions appear to be directed at relatively atrial-selective potassium currents, which result in lengthening of the atrial action potential and prolongation of the atrial action potential plateau, while not significantly affecting the Q-T interval or the ventricular effective refractory period. As a result, the proarrhythmic effects observed with all other agents approved by FDA for the treatment of AF are eliminated. In clinical trials of vernakalant versus placebo, a statistically significant number of patients converted to normal sinus rhythm after receiving vernakalant. For patients with atrial fibrillation continuing for 3–72 hours, the median time to conversion was between 8 and 14 minutes, with 79% of those who converted remaining in sinus rhythm at 24 hours.
Conclusion. Intravenous vernakalant, a novel, relatively atrial-selective antiarrhythmic agent, appears to offer an effective and safe approach to the rapid conversion of recent-onset AF to normal sinus rhythm.
Index terms Atrial fibrillation; Cardiac drugs; Mechanism of action; Pharmacokinetics; Toxicity; Vernakalant
Introduction
Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, contributes to an increasing number of emergency room visits and hospital admissions. In 2001, it was estimated that 2.3 million U.S. adults had been diagnosed with AF; this number was projected to grow to more than 5.6 million by 2050. A more recent estimate places the number at 15.9 million by 2050. The financial burden of AF is estimated at $6.65 billion annually in the United States.
Increased morbidity and mortality are observed in patients with AF. Sequelae of AF include precipitation or worsening of heart failure, symptoms such as dyspnea and palpitations, and thromboembolic events. Patients with AF have a fivefold increased risk of ischemic stroke. Approximately 50,000 ischemic strokes are associated with AF in the United States each year.
The prevalence of AF increases dramatically with age. The prevalence is only 0.1% in adults less than 55 years of age, compared with 9% in those 80 years of age and older. The prevalence and financial burden are expected to continue to increase as the population ages.