(Circulation. 1996;94:2535-2541.)
© 1996 American Heart Association, Inc.
Articles |
Sex Difference in Risk of Torsade de Pointes With d,l-Sotalol
the Arrhythmia Center, Department of Medicine/Division of Cardiology, Sinai Hospital, Detroit, Mich (M.H.L.), and Bristol-Myers Squibb Co, Princeton, NJ (S.H., D.A., B.Q., D.J.M.).
Correspondence to Michael H. Lehmann, MD, Arrhythmia Center/Sinai Hospital, 14800 W McNichols, Suite 314, Detroit, MI 48235.
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.
Methods and 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.
Key Words: antiarrhythmia agents • death, sudden • sex • torsade de pointes • women
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