Concomitant Use of Quinolones and Stimulants and the Risk of Adverse Cardiovascular Symptoms: A Retrospective Cohort Study

OBJECTIVE: To examine whether concomitant use of quinolones and stimulants increases the risk of cardiac events in adults. STUDY DESIGN: A retrospective cohort study of privately insured adults using MarketScan((R)) claims data from 2008 to 2015. PATIENTS: Stimulant (methylphenidate or mixed amphetamine salts) users (18-65 yrs old) with continuous health plan enrollment for the 6 months (baseline) prior to the first dispensation (index date) of oral quinolones or comparators (amoxicillin +/- clavulanate or azithromycin). OUTCOMES DEFINITION: (1) Cardiac symptoms (palpitation, tachycardia, or syncope); (2) cardiac arrhythmias (ventricular arrhythmias, paroxysmal ventricular tachycardia, or cardiac arrest). ANALYSIS: Baseline covariates adjustment was through inverse probability of treatment weighting. Adults were followed until the antimicrobial therapy ended. The hazard of cardiac events in stimulant-quinolones-exposed adults was compared to those who were treated with stimulant-comparator antibiotics using a weighted Cox regression model. Several sensitivity analyses were performed to challenge the results robustness. RESULTS: The study cohorts comprised 390,490 stimulants users who initiated either quinolone or amoxicillin, and 387,574 patients receiving stimulants who initiated quinolone or azithromycin. The unadjusted incidence rate for cardiac symptoms in stimulant-quinolones users was 471 cases/10,000 patient-years, and it was 244 cases/10,000 patient-years in patients exposed to stimulant-amoxicillin; whereas the unadjusted incidence rate for cardiac symptoms was 728 and 358 per 10,000 patient-years for stimulant-quinolones and stimulant-azithromycin cohorts, respectively. Compared to stimulant-amoxicillin use, the adjusted hazard ratio (HR) for cardiac symptoms with stimulant-quinolones use was 1.61 (95% confidence interval [CI], 1.30-1.98). The HR for cardiac symptoms for patient exposed to stimulant-quinolones was 1.69 (95% CI, 1.32-2.13) when compared to stimulant-azithromycin. The sensitivity analysis findings were consistent with the primary analysis. A few patients across the study comparison groups developed cardiac arrhythmias. CONCLUSION: Concomitant use of stimulants and quinolone was associated with an increased hazard of cardiac symptoms in comparison to concomitant use of stimulants and amoxicillin or azithromycin, but there was no apparent difference in cardiac arrhythmias.