Efficacy of gemfibrozil in the primary prevention of atrial fibrillation in a large randomized controlled trial

A. Selcuk Adabag, Salima Mithani, Basel Al Aloul, Dorothea Collins, Stefan Bertog, Hanna E. Bloomfield

Research output: Contribution to journalArticlepeer-review

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Abstract

Background: Peroxisome proliferator-activated receptor α (PPARα) activators reduce inflammation and oxidative stress. Inflammation plays an important role in the initiation and maintenance of atrial fibrillation (AF). It has been suggested that PPARα activators may have antiarrhythmic properties, but no clinical data exist. The objective of this study was to investigate whether the PPARα activator gemfibrozil prevents or delays the development of AF in patients with coronary heart disease. Methods: We retrospectively analyzed the electrocardiograms (ECGs) performed in the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial, a multicenter, randomized, double-blinded, secondary prevention trial of gemfibrozil and matching placebo. The ECGs were performed annually or biannually and when clinically indicated. Participants who were in AF on baseline ECG were excluded from the present analysis. Relative risk for AF was calculated from Cox regression with death as a competing risk factor. Results: A total of 12,605 ECGs from 2,130 participants were interpreted (5.9 ± 2.1 ECGs per participant, range 2-20). At baseline, the gemfibrozil (n = 1,070) and placebo (n = 1,060) groups were well matched. Mean age was 64.1 ± 7.1 years. Over 4.4 ± 1.5 years of follow-up, 123 (5.8%) participants developed new AF. There was no difference in AF incidence between the gemfibrozil and placebo groups (64/1,070 vs 59/1,060, respectively; P = .33). In Cox regression, the risk of AF was similar between the 2 study groups (hazard ratio 1.04, 95% CI 0.73-1.49, P = .82). Conclusions: In this post hoc analysis of a multicenter, double-blinded, randomized controlled trial, the PPARα activator gemfibrozil did not reduce the 4-year incidence of AF among men with coronary heart disease.

Original languageEnglish (US)
Pages (from-to)913-918
Number of pages6
JournalAmerican Heart Journal
Volume157
Issue number5
DOIs
StatePublished - May 2009

Bibliographical note

Funding Information:
This study was approved by the human studies subcommittee of the Research and Development committee at the Minneapolis Veterans Affairs Medical Center. Individual consent was waived. This work was supported by a grant from the Minneapolis Veterans Research Institute and the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper, and its final contents.

Funding Information:
Dr Adabag is supported, in part, by Veterans Affairs Clinical Science Research and Development Service (grant 04S-CRCOE 001), Washington, DC. Drs Mithani and Aloul have invested equal effort in this project.

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