Abstract
Background
We sought to determine whether insulin-sensitizing therapy (thiazolidinediones or
metformin) decreased the risk of developing atrial fibrillation compared with insulin-providing
therapy (insulin, sulfonylurea, or a meglitinide). Thiazolidinediones are insulin
sensitizers that also decrease the inflammatory response. Because 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 insulin-sensitizing therapy or insulin-providing therapy.
Results
A total of 2319 patients entered the study, with 1160 assigned to the insulin-sensitization
strategy and 1159 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 1000 person-years in patients
assigned to insulin sensitization compared with 9.5 in patients assigned to insulin
provision with a hazard ratio (HR) of 0.91 (95% confidence interval [CI], 0.60-1.38,
P = .66). In a time-varying exposure analysis, the incidence rate per 1000 person-years
was 7.2 while exposed to thiazolidinediones and 9.7 while not exposed to thiazolidinediones
with an adjusted HR of 0.80 (95% CI, 0.33-1.94, P = .62). In a subset of patients matched on propensity to receive a thiazolidinediones,
the HR was 0.75 (95% CI, 0.43-1.30, P = .30).
Conclusions
We did not find a significant reduction of atrial fibrillation incidence with use
of thiazolidinediones.
Keywords
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Article info
Publication history
Published online: March 26, 2018
Footnotes
Funding: The original Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) was funded by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases (U01 HL061744, U01 HL061746, U01 HL061748, U01 HL063804, R21HL121495). The original BARI 2D received support from the following companies: GlaxoSmithKline; Lantheus Medical Imaging, Inc (formerly Bristol-Myers Squibb Medical Imaging, Inc); Astellas Pharma US, Inc; Merck & Co., Inc; Abbott Laboratories, Inc; Pfizer, Inc; MediSense Products; Bayer Diagnostics; Becton, Dickinson and Company; cJ. R. Carlson Labs; Centocor, Inc; Eli Lilly and Company; LipoScience, Inc; Merck Sante; Novartis Pharmaceuticals Corporation; and Novo Nordisk, Inc. JLP has received research funding from Boehringer-Ingelheim and Bayer. MMB has received a research grant from Gilead Sciences Inc. BC has received consult fees from Lilly, Novo Nordisk, and Merck outside the submitted work.
Conflicts of Interest: None.
Authorship: All authors had access to the data and played a role in writing this manuscript.
Identification
Copyright
© 2018 Elsevier Inc. All rights reserved.
