Thiazolidinediones and Risk of Atrial Fibrillation among Patients with Diabetes and Coronary Disease

Abstract Purpose We sought to determine whether insulin-sensitizing therapy (thiazolidinediones and/or metformin) decreased risk of developing atrial fibrillation compared with insulin-providing therapy (insulin, sulfonylurea, and/or a meglitinide). Background Thiazolidinediones are insulin-sensitizers that also decrease the inflammatory response. Since inflammation is a risk factor for atrial fibrillation, we hypothesized that treating diabetes with thiazolidinediones might decrease the risk of developing atrial fibrillation. Methods The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial enrolled patients with type 2 diabetes and documented coronary artery disease. All patients were randomized to either insulin-sensitizing therapy or insulin-providing therapy. Results A total of 2,319 patients entered the study, with 1,160 assigned to the insulin-sensitization strategy, and 1,159 assigned to the insulin-provision strategy. Over a median follow-up of 4.2 years, 90 patients (3.9%) developed new onset atrial fibrillation. In the intention-to-treat analysis, the incidence of atrial fibrillation was 8.7 per 1,000 person years in patients assigned insulin-sensitization, compared with 9.5 in patients assigned to insulin-provision with an hazard ratio of 0.91 (95% confidence interval of 0.60 to 1.38, p=0.66). In a time-varying- exposure analysis, the incidence rate per 1,000 person years was 7.2 while exposed to thiazolidinediones and 9.7 while not exposed to thiazolidinediones with an adjusted hazard ratio of 0.80 (95% confidence interval 0.33 to 1.94, p=0.62). In a subset of patients matched on propensity to receive a thiazolidinediones, the hazard ratio was 0.75 (95% confidence interval 0.43 to 1.30, p=0.30). Conclusions Our findings suggest no significant reduction of atrial fibrillation incidence with use of thiazolidinediones.