QTc Prolongation in Patients Receiving Triazoles and Amiodarone

BACKGROUND: Prolonged QT interval may lead to ventricular arrhythmias, torsade de pointes and sudden death. Triazole antifungals are often administered to inpatients with cardiac disease and with other QT prolonging drugs. Amiodarone is a commonly used antiarrhythmic that can prolong QT and be proarrhythmic but safety of co-administering these agents in the clinical setting is not known. METHODS: We conducted a retrospective, observational cohort study of adult inpatients at Duke University Medical Center who received concomitant systemic azoles and amiodarone from 2007 to 2013. Included subjects had ≥1 electrocardiogram (EKG) performed while receiving either agent alone within 1 month of starting concomitant therapy (baseline, BL) and ≥1 follow-up (FU) EKG after ≥2 days of concomitant therapy. A paired t-test was used to assess the maximum change in corrected QT interval (QTc, Bazett’s correction) from BL to FU. Logistic regression was used to evaluate predictors of FU QTc ≥500 ms (age, race, gender, and BL QTc ≥500 ms). Patient discharge diagnoses of ventricular arrhythmias or other cardiac events were reviewed to assess clinical outcome. RESULTS: Of 816 subjects identified, 252 had EKG results eligible for analysis. Azoles received were fluconazole (86.5%), voriconazole (11.5%), posaconazole (1.6%) or itraconazole (0.4%). Subjects were a median of 65 (IQR 25–88) years of age, 64.3% male and 78.6% Caucasian. Median duration of concomitant therapy was 7 days (IQR 4–11 days). Mean maximal change in QTc was +32 ms from BL (95% CI 26.2–38.6, P < 0.0001). 25.4 and 48.8% of subjects had a BL and FU QTc ≥500 ms, respectively. BL QTc ≥500 ms but not age, race, or gender was associated with FU QTc ≥500 ms (OR 6.32 95% CI 3.21–12.43). Thirty-day all-cause mortality was 26.2%. No cardiac events were apparent in relation to concomitant azole-amiodarone therapy. CONCLUSION: Prolongation of the QTc interval was frequently observed in this cohort of patients receiving azoles and amiodarone. Clinical impact is challenging to assess in this critically ill, complex patient population but appears to be limited. Additional analyses are needed to further evaluate safety of azoles in the setting of other QTc prolonging agents. DISCLOSURES: All authors: No reported disclosures.