Findings from a recent retrospective pharmacovigilance disproportionality analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) database revealed several previously unknown drug-associated cardiac arrhythmias.
To identify medications with potential proarrhythmic associations other than QTc prolongation, the study authors created a large dataset combining FAERS reports published between 2004 and 2019. “Frequency of the cardiac arrhythmias were determined for atrial fibrillation, atrioventricular block, bradyarrhythmia, bundle branch block, supraventricular tachycardia, and ventricular fibrillation and linked to the reported causal medications,” the authors stated.
Additionally, package inserts and drug databases were utilized to further categorize the reports according to prior evidence associations. Reporting odds ratios (RORs) and confidence intervals (CIs) were reported for adverse drug reactions (ADRs) for each medication as well as for each of the cardiac arrhythmias.
Of the total 11.6 million FAERS reports in the dataset, 68,989 were found to be specific to the arrhythmias of interest. “There were 61 identified medication-reported arrhythmia pairs for the 6 arrhythmia groups with 33 found to have an unknown reported association,” the study authors reported.
Findings of the analysis revealed rosiglitazone to be the most frequently reported medication across all arrhythmias (ROR, 6.02; CI, 5.82-6.22). The analysis also showed rofecoxib, digoxin, alendronate, lenalidomide, dronedarone, zoledronic acid, adalimumab, dabigatran, and interferon beta-1b to be associated with significant findings as well.
“Upon retrospective analysis of the FAERS database, the majority of drug-associated arrhythmias reported were unknown suggesting new potential drug causes,” the study authors concluded. They added that while the FAERS database cannot be used to determine causal relationships, it should be considered a “timely pharmacovigilance tool” that can be incorporated in future studies examining unknown ADRs.
Moreland-Head LN, Coons JC, Seybert AL, Gray MP, Kane-Gill SL. Use of disproportionality analysis to identify previously unknown drug-associated causes of cardiac arrhythmias using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. J. Cardiovasc. Pharmacol. Ther. In press.