JTc prolongation with d,l-sotalol in women versus men

Women are at increased risk for torsades de pointes associated with a varie ty of drugs that prolong ventricular repolarization, but few data exist reg arding possible sex differences in extent of repolarization changes with th ese medications. We sought to compare JTc interval responses in women and m en during treatment with d,l-sotalol. The study cohort consisted of 1,897 p atients (26% women) with available baseline and greater than or equal to 1 on-drug electrocardiogram from a database involving patients exposed to ora l d,l-sotalol without developing torsades de pointes. The mean lowest and h ighest daily d,l-sotalol dose, normalized for weight was not significantly different between sexes. At each dosing extreme, on-drug JTc was significan tly longer in women (p less than or equal to 0.0002). Statistically indepen dent predictors of on-drug JTc included gender (p = 0.003), baseline JTc (p = 0.0001) dose (p = 0.0001), serum creatinine (p less than or equal to 0.0 3), and history of sustained ventricular tachyarrhythmias (p = 0.01). In bo th men and women, as baseline JTc increased, the drug-induced increment in JTc became progressively smaller. Thus, in response to d,l-sotalol, JTc int ervals become longer in women than in men. This sex difference is independe nt of dose and not solely attributable to the known gender disparity in bas eline JTc. The greater propensity of women to drug-induced torsades de poin tes may represent the most extreme expression of a basic sex difference in the response to medications that prolong ventricular repolarization. (C)199 9 by Excerpta Medico, Inc.