Analysis of the US FDA adverse event reporting system to identify adverse cardiac events associated with hydroxychloroquine in older adults.

PURPOSE: The purpose of this study is to analyze the US FDA Adverse Event Reporting System (FAERS) to identify adverse cardiac events of hydroxychloroquine in older adults. METHOD: A case/non-case method was used to determine adverse events associated with hydroxychloroquine as the primary suspect drug between January 1, 2004, and December 31, 2019, for older adults (≥65 years). Adverse events are preferred terms (PTs) defined in MedDRA. We used frequentist approaches, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) to measure disproportionality. We used Bayesian approaches to derive information component (IC) value and Empirical Bayesian Geometric Mean (EBGM) score. Signals were defined as the number of reports > 3 and the lower limit of 95% confidence intervals (CI) of ROR ≥ 2, PRR ≥ 2, IC > 0, EBGM > 1. RESULTS: We identified 334 adverse cardiac events comprising 71 different MedDRA PTs from 2004 to 2019 for hydroxychloroquine in older adults. Strong disproportionality signals were noted for "Restrictive cardiomyopathy" (ROR = 272.43 (138.09-537.47); EBGM = 149.78 (77.34-264.67), "Right ventricular hypertrophy" (219.49 (85.32-564.70); 102.74 (39.67-222.81), "Cardiac septal hypertrophy" (226.77 (78.65-653.80); 93.82 (32.19-219.81), "Myocardial fibrosis" (57.29 (21.06-155.85); 42.99 (14.74-100.75), and "Cardiotoxicity" (43.90 (26.66-72.27); 40.28 (24.02-63.72). CONCLUSIONS: The risk of cardiomyopathy and myocardial disorders is high following exposure to hydroxychloroquine in older adults. Due to the current lack of safety data from randomized controlled trials as well as large observational studies to confirm the risk of adverse cardiac events associated with hydroxychloroquine, findings from analyses of post-marketing data may serve as interim guidance.