Efficacy of gemfibrozil in the primary prevention of atrial fibrillation in a large randomized controlled trial.
BACKGROUND
Peroxisome proliferator-activated receptor alpha (PPARalpha) 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 PPARalpha activators may have antiarrhythmic properties, but no clinical data exist. The objective of this study was to investigate whether the PPARalpha 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 PPARalpha activator gemfibrozil did not reduce the 4-year incidence of AF among men with coronary heart disease.
Division of Cardiology, Center for Chronic Disease Outcomes Research, Veterans Affairs Medical Center, Minneapolis, MN, USA. adaba001@umn.edu
A Selcuk
AS
Adabag
Salima
S
Mithani
Basel
B
Al Aloul
Dorothea
D
Collins
Stefan
S
Bertog
Hanna E
HE
Bloomfield
D000368:Aged; D001281:Atrial Fibrillation / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D003327:Coronary Disease / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D015248:Gemfibrozil / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D011322:Primary Prevention / Q000379:methods*; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D015248:Gemfibrozil