title: Sex difference in risk of torsade de pointes with d,l-sotalol.
abstract: BACKGROUND
  The present study was undertaken to test the hypothesis that women are more prone than men to develop torsade de pointes (TdP) in a defined cohort of patients exposed to the QT-prolonging antiarrhythmic drug d,l-sotalol.
  
  
  RESULTS
  In a database derived from 22 clinical trials involving 3135 adult patients who received oral d,l-sotalol (median follow-up, 164 days), TdP developed in 44 (1.9%) of 2336 men and in 33 (4.1%) of 799 women (P < .001). Logistic regression analysis identified female sex (P < .0001), presenting arrhythmia of sustained ventricular tachycardia or fibrillation (P < .0001), history of congestive 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 creatinine > 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 risk 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 d,l-sotalol. This finding needs to be taken into account, together with other TdP risk factors, when patients are treated with this antiarrhythmic agent. Given the consistency between the present and other recent observations, greater caution in women regarding use of QT-prolonging drugs, in general, is advisable.
authors.affiliation: Department of Medicine/Division of Cardiology, Sinai Hospital, Detroit, Mich 48235, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Lehmann
authors.forename: S
authors.initials: S
authors.lastname: Hardy
authors.forename: D
authors.initials: D
authors.lastname: Archibald
authors.forename: B
authors.initials: B
authors.lastname: quart
authors.forename: D J
authors.initials: DJ
authors.lastname: MacNeil
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007256:Information Systems; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D012727:Sex Characteristics; D017678:Sex Distribution; D013015:Sotalol / Q000009:adverse effects*; D013997:Time Factors; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000453:epidemiology
chemical_list: D000889:Anti-Arrhythmia Agents; D013015:Sotalol