An evaluation of co-use of chloroquine or hydroxychloroquine plus azithromycin on cardiac outcomes: A pharmacoepidemiological study to inform use during the COVID19 pandemic

Abstract

BackgroundChloroquine or hydroxychloroquine (chloroquine) plus azithromycin is considered as therapy for COVID-19. With benefit evaluations underway, safety concerns due to potential additive effects on QTc prolongation should be addressed.ObjectiveWe compared risk of cardiac adverse events between combinations of chloroquine and azithromycin and chloroquine and amoxicillin.MethodsWe conducted a retrospective cohort study using the IBM MarketScan Commercial Claims and Medicare Supplemental Databases, 2005–2018. We included autoimmune disease patients aged ≥18 years initiating azithromycin or amoxicillin for ≥5 days during chloroquine treatment. Patients had continuous insurance coverage ≥6 months before combination use until 5 days thereafter or inpatient death. Two outcomes were sudden cardiac arrest/ventricular arrhythmias (SCA/VA) and cardiac symptoms. We followed patients for up to 5 days to estimate hazard ratios (HR). Covariates were adjusted using stabilized inverse probability treatment weighting.ResultsWe identified two SVC/VA events among >145,000 combination users. The adjusted incidence of cardiac symptoms among azithromycin and amoxicillin users was 276 vs 254 per 10,000 person-years with an adjusted HR of 1.10 (95%CI, 0.62–1.95).ConclusionCombination use of chloroquine and azithromycin at routine doses did not show pronounced increases in arrhythmias in this real-world population, though small sample size and outcome rates limit conclusions.