Association Between Pioglitazone Use and Risk of Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus and Stable Coronary Artery Disease: A Retrospective Analysis From the North Florida Region

Background and Objectives: Diabetes mellitus (DM) and coronary artery disease (CAD) are strongly associated with atrial fibrillation (AF) and its complications.The pathophysiology linking DM and CAD to AF is related to metabolic derangements that lead to atrial remodeling, such as oxidative stress, systemic inflammation, and atrial hypoxia.Thiazolidinediones are anti-diabetic medications with anti-inflammatory and anti-fibrotic effects.The aim of this study was to investigate whether pioglitazone exposure in patients with type 2 DM and stable CAD is associated with decreased AF occurrence.Methods: This retrospective analysis included adult patients presenting to hospitals within the North Florida division between January 1, 2021 and December 31, 2022.Patients with type 2 DM and stable CAD were identified (n=74,430), and 38,151 patients were included.Of these, 1,055 were taking pioglitazone.The association between pioglitazone exposure and AF occurrence was analyzed using the χ 2 test of proportions.Covariates contributing to AF were evaluated using logistic regression with Firth's penalized likelihood.Significance was set at p<0.05.Results: Pioglitazone exposure was associated with lower odds of AF occurrence (odds ratio [OR], 0.846; 95% confidence interval [CI], 0.719-0.991;p=0.038).Male sex was associated with increased odds of AF (OR, 1.220; 95% CI, 1.157-1.287;p<0.001).In addition, chronic kidney disease, obstructive sleep apnea, cirrhosis, and alcohol use were significantly associated with AF.Conclusions: Pioglitazone exposure was associated with decreased AF occurrence in patients with DM and stable CAD.Underlying mechanisms warrant further investigation.