Gender differences in the proarrhythmic potential of QT-prolonging drugs

Female gender is associated with an increased risk of torsades de pointes (TDP) in the setting of drugs that can prolong the QT interval. These drugs are all potassium channel blocking agents and include many frequently used antiarrhythmic drugs, as well as a variety of noncardiac medications. The mechanism of this gender difference is unknown. Some women at risk are silent carriers of the long QT syndrome. The concept of "repolarization reserve" can help predict which individuals are at risk for developing drug-induced TDP. Generic formulations of QT-prolonging drugs have the potential to increase proarrhythmic risk to women. Female subjects need to be well represented in the testing of new potassium channel blocking drugs.