Dofetilide dose reductions and discontinuations in women compared with men.

BACKGROUND: Compared with men, women have longer corrected QT (QTc) intervals, lower clearance of dofetilide, and higher rates of drug-induced torsades de pointes, but the dofetilide dosing algorithm is the same for men and women. OBJECTIVE: The purpose of this study was to evaluate the tolerability of the 500 µg twice daily dose of dofetilide for men and women. METHODS: Men and women admitted to Duke University Medical Center (January 1, 2006, to October 19, 2012) for the initiation of dofetilide 500 µg twice daily were matched 1:1 on age and estimated creatinine clearance. Electrocardiograms throughout dosing were analyzed, and rates of dofetilide discontinuations and dose reductions were compared in unadjusted and adjusted analyses. RESULTS: For 220 matched men and women, the median age was 62.5 years (interquartile range 55-69 years) and the median eCrCl was 98.1 mL/min (interquartile range 77.6-126.2 mL/min). Women were less likely than men to have hypertension and interventricular conduction delay but were otherwise similar. During dofetilide initiation, women were more likely than men to have their dofetilide dose discontinued or reduced (55% vs 32%; P < .001). In most women (82%) and men (69%), the reason for dose adjustment was significant QTc prolongation. In the adjusted analysis, female sex was associated with higher rates of dofetilide dose discontinuations or reductions (odds ratio 3.01; 95% confidence interval 1.58-5.71; P < .01). CONCLUSION: More than half of women who initiated on 500 µg twice daily of dofetilide required medication discontinuations or dose reductions, mostly because of QTc prolongation. Additional studies are needed to evaluate the optimal dosing algorithm of dofetilide in women.

Positive Impact of Continuous-Flow Left Ventricular Assist Device Implantation on Glycemic Control in Patients with Type 2 Diabetes Mellitus and Advanced Chronic Systolic Heart Failure.

STUDY OBJECTIVE: To evaluate the impact of continuous-flow left ventricular assist device (LVAD) implantation on glycemic control in patients with type 2 diabetes mellitus and advanced chronic systolic heart failure. DESIGN: Retrospective medical record review. SETTING: Large academic tertiary and quaternary care hospital. PATIENTS: Eighty-three adults with type 2 diabetes mellitus and advanced chronic systolic heart failure who underwent implantation of a continuous-flow LVAD between July 1, 2008, and June 30, 2013. MEASUREMENTS AND MAIN RESULTS: Baseline demographic data and laboratory values pertinent to glycemic control (hemoglobin A1c [A1C], total daily insulin requirements, noninsulin antidiabetic medication use, and body mass index [BMI]) were collected for each patient. Pre-LVAD data were compared with data obtained during the 24 months after LVAD implantation. The mean age of the study population was 61.3 years, 70% were men, and 63% had ischemic cardiomyopathy. The first available mean ± SD A1C after LVAD implantation was 6.21 ± 1.5% at a median of 4.8 months (interquartile range 3.3-8.9), which represented a significant decrease from the pre-LVAD A1C of 7.46 ± 1.5% (p<0.001). Average daily insulin requirements decreased by 22.9 units at the end of 24 months (p<0.001). Over half of patients with prescriptions for noninsulin antidiabetic medications were able to discontinue therapy by the end of the study. Of note, BMI increased in the second year after LVAD implantation from a baseline of 32.3 kg/m2 to 34.9 kg/m2 (p=0.004). Regression analysis revealed that baseline A1C was the only independent predictor of change in A1C. CONCLUSION: LVAD implantation was associated with a significant improvement in glycemic control. Further prospective studies are needed to evaluate the long-term impact of LVAD implantation on the clinical course of diabetes.