Using Medicare Data to Assess the Proarrhythmic Risk of Non-Cardiac Treatment Drugs that Prolong the QT Interval in Older Adults: An Observational Cohort Study.

ABSTRACT

INTRODUCTION: Serious cardiac arrhythmias caused by QT-prolonging drugs are difficult to predict based on physiological measurement and pre-approval clinical trials. Post-marketing surveillance and monitoring are important to generate safety data. OBJECTIVES: To assess whether an observational study using Medicare claims data can detect the arrhythmogenic risk of QT-prolonging drugs. METHODS: We identified 17 QT-prolonging drugs with known risk of torsades des pointes (TdP) that were not used to treat cardiac arrhythmias. Amoxicillin and four serotonin-norepinephrine reuptake inhibitors (SNRIs) were used as controls. De-identified claims data of 1.2 million Medicare beneficiaries were accessed. Two separate Cox regressions were done for short-term and chronic-use drugs. The primary outcome was a composite of ventricular arrhythmias and/or sudden death, identified by ICD diagnostic codes. We explored the independent effect of each study drug on the outcomes. Other covariates included patient demographics, comorbidities, and known risk factors for drug-induced cardiac arrhythmia. RESULTS: We were able to detect increased risk in 14 of 17 study drugs (82.3%), and none of the control drugs. Among the fluoroquinolones, ciprofloxacin was the safest. Azithromycin and clarithromycin were relatively safe compared to erythromycin. Compared to SNRIs, both citalopram and escitalopram had increased risk, more so with escitalopram than citalopram. Comorbidities associated with increased risk included ischemic heart disease, electrolyte imbalance, bradycardia, acute myocardial infarction, heart failure, and chronic kidney and liver disease. CONCLUSION: Medicare data can be utilized for post-marketing surveillance and monitoring of the proarrhythmic risk of QT-prolonging drugs in older adults.