SEX DIFFERENCE IN RISK OF TORSADE-DE-POINTES WITH D,L-SOTALOL

Background The present study was undertaken to test the hypothesis tha t women are more prone than men to develop torsade de pointes (TdP) in a defined cohort of patients exposed to the QT-prolonging antiarrhyth mic drug d,l-sotalol. Methods and Results In a database derived from 2 2 clinical trials involving 3135 adult patients who received oral d,l- sotalol (median follow-up, 164 days), TdP developed in 44 (1.9%) of 23 36 men and in 33 (4.1%) of 799 women (P<.001). Logistic regression ana lysis identified female sex (P<.0001), presenting arrhythmia of sustai ned ventricular tachycardia or fibrillation (P<.0001), history of cong estive heart failure (P<.001), and d,l-sotalol dose >320 mg/d (P<.001) as factors most predictive of TdP; in addition to these, a serum crea tinine >1.4 mg/dL in women and >1.6 mg/dL in men was weakly predictive (P<.05). After adjustment for these risk factors, women had threefold greater odds of developing TdP than men. The sex difference in TdP ri sk was age independent and could not be explained by differential dose -related bradycardic responses in women versus men. Conclusions Women are at increased risk of developing TdP during administration of dl-so talol. This finding needs to be taken into account, together with othe r TdP risk factors, when patients are treated with this antiarrhythmic agent. Given the consistency between the present and other recent obs ervations, greater caution in women regarding use of QT-prolonging dru gs, in general, is advisable.