Increased Cardiac Risk With Concomitant Levofloxacin (LVQ) and Amiodarone (AMIO) Therapy

Background: LVQ and AMIO both prolong the QT interval. Case reports have highlighted the potential cardiac effects with concomitant use; however, no studies validating this concern have been completed in a real-world, clinical setting.

Methods: A retrospective study of patients treated with LVQ and AMIO discharged from the medical center from January 1, 2012 to August 31, 2015 was performed. Inclusion was limited to patients ≥18 years of age. Patients on acute AMIO therapy immediately upon admission were excluded from the study. Patients were stratified into two groups: concomitant and non-concomitant usage of levofloxacin and amiodarone. The groups were further balanced using 2:1 propensity score matching based on age, gender, race, and Charlson comorbidity index. A secondary subset analysis was completed for patients with QT measurements before and after therapy initiation. The primary outcome was occurrence of cardiac events (ventricular arrhythmia, cardiac death) identified using validated ICD-9 codes and verified through patient chart review. The secondary outcome was change in adjusted QT interval (QTc) from baseline to post-treatment.

Results: A total of 228 patients were included; 152 received concomitant LVQ and AMIO. Patients who received concomitant therapy were 6.6 times more likely to experience a cardiac event versus either LVQ or AMIO alone (15.1% versus 2.6%; OR=6.6, 95% confidence interval [CI] 1.74 – 42.3; p=0.004). All cause mortality was similar between concomitant vs the non-concomitant group (9.9% vs 9.2%, respectively; p=ns). The secondary analysis included 102 patients, 71 received concomitant LVQ and AMIO. There was a mean change from baseline in QTc interval of 30.54 milliseconds (ms) for the concomitant group and -0.50 ms for the non-concomitant group (mean difference, 31.03 ms; p<0.0001; 95% CI, 18.28 ms, 43.79 ms).

Conclusion: A statistically significant increase in cardiac events and QTc interval prolongation was found in patients given concomitant LVQ and AMIO versus either medication alone.