Celecoxib-induced change in atrial electrophysiologic substrate in arthritis patients.
BACKGROUND
Cyclooxygenase-2 inhibitors, the newest class of nonsteroidal antiinflammatories, pose an increased risk of adverse cardiovascular events, in particular atrial fibrillation (AF). We hypothesized that the COX-2 inhibitor celecoxib alters atrial electrophysiology, and thus promotes the development of AF.


METHODS
Three prospective patient cohorts were created: Healthy patients (n = 35), inflammatory arthritis patients with no celecoxib use (n = 22), and inflammatory arthritis patients treated with celecoxib (n = 20). Patients were included in the arthritis cohorts if they were over the age of 18 and had a diagnosis of inflammatory arthritis. Patients in the celecoxib group must be actively treated with celecoxib for more than 2 months. Patients were excluded if they were taking antiarrhythmic mediation, had a diagnosis of AF, refractory hypertension, or congestive heart failure. High-resolution signal-averaged electrocardiogram was recorded and P-wave duration (PWD) was derived.


RESULTS
PWD was significantly longer in inflammatory arthritis patients treated with celecoxib, compared to both healthy and inflammatory arthritis patients (P = 0.049, P = 0.036). There was no difference in the PWD of healthy patients as compared to inflammatory arthritis patients (P = 0.916). Mean PWD (standard error of the mean) of the inflammatory arthritis patients treated with celecoxib was 133.1 (2.7) ms as compared to 125.3 (1.6) ms in the healthy patients and 124.0 (2.9) ms in the inflammatory arthritis patients.


CONCLUSIONS
Given that PWD is a well-accepted noninvasive marker of atrial electrophysiology, our results suggest that these patients demonstrate adverse atrial remodeling predisposing to atrial arrhythmia.
Queen's University, Kingston, Ontario, Canada.
Katerina
K
Pizzuto
Henry L
HL
Averns
Adrian
A
Baranchuk
Hoshiar
H
Abdollah
Kevin A
KA
Michael
Christopher
C
Simpson
Damian P
DP
Redfearn
D000704:Analysis of Variance; D001168:Arthritis / Q000188:drug therapy*; D001281:Atrial Fibrillation / Q000139:chemically induced*; D000068579:Celecoxib; D015331:Cohort Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D004562:Electrocardiography / Q000187:drug effects* / Q000379:methods / Q000706:statistics & numerical data; D005260:Female; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011720:Pyrazoles / Q000009:adverse effects* / Q000627:therapeutic use; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib
P-wave duration; atrial fibrillation; inflammatory arthritis