Abstract Body (Do not enter title and authors here): Introduction: Atrial fibrillation (AF) and coronary artery disease (CAD) has a strong association. Diabetes Mellitus (DM) is also a known risk factor for the development of AF and the severity of DM is almost directly correlated with worsening AF burden. Thiazolidinediones (TZDs) are a treatment option in DM that have been found to decrease risk of developing AF in certain populations.

Hypothesis: We hypothesized that the use of pioglitazone in patients with DM and stable CAD decreases the odds of developing AF and development of rapid ventricular response (RVR) in patients with AF.

Methods: We identified adult patients presenting to any Hospital Corporation of America (HCA) facility within the North Florida division with a diagnosis of Type II DM and stable CAD between 01/01/2021 and 12/31/2022 (N=38,151). A cohort of patients with documented pioglitazone usage (N=1,055) compared AF rates against those with no documented pioglitazone usage using a Chi-Square Test of Proportions. We also examined a cohort of patients with documented pioglitazone usage (N=197) who had diagnosed AF with RVR against those no documented pioglitazone usage using a Chi-Square Test of Proportions. In addition, multiple covariates that contribute to the development of AF and AF with RVR were evaluated using Logistic Regression with Firth’s Penalized Likelihood.

Results: We find evidence that pioglitazone usage is associated with 0.846 lower odds of developing AF (95% CI 0.719-0.991, p<0.038). However, within patients with established AF, pioglitazone use is not associated with decreased odds of developing RVR. Odds of AF and AF with RVR increase if the patient is diagnosed with chronic kidney disease, obstructive sleep apnea, cirrhosis, and alcohol use disorders, regardless of pioglitazone usage.

Conclusion: Based on the results of this study, use of pioglitazone was associated with decreased odds of developing atrial fibrillation. However, when we control for various factors, we do not see a difference in rates of developing RVR in patients with AF taking pioglitazone versus those not taking pioglitazone. Further research is needed to establish if there is a synergistic role to other anti-diabetic medications that lower risk of AF.