Risk of proarrhythmia with class III antiarrhythmic agents: sex-based differences and other issues.

Although men have a higher risk of atrial fibrillation compared with women, the absolute number of women with atrial fibrillation is greater. Congestive heart failure increases the risk of developing atrial fibrillation in women more than in men, and the prognosis for women with atrial fibrillation is worse than for men. The longer baseline corrected QT interval in women is well known. The mechanism is likely the result of increased circulating androgens, causing the QT interval to shorten in men after puberty. Female sex is associated with an increased risk of torsades de pointes in the setting of potassium antagonists. Class III antiarrhythmic drugs are frequently used for the treatment of atrial fibrillation in heart failure patients because of their neutral effect on mortality and their tolerance by patients with low ejection fractions. Although amiodarone and azimilide carry a low potential for producing torsades de pointes compared with sotalol and dofetilide, the prevalence of torsades de pointes in women is at least twice that in men for all these drugs. Careful monitoring of the QT interval and potassium level, as well as control of congestive heart failure, can help reduce the risk of proarrhythmia. Avoidance of polypharmacy with other potassium antagonists and unmonitored drug formulation changes are important in the management of all patients taking class III agents, but they are particularly crucial in women with additional risk factors for torsades de pointes.