Incidence and possible risk factors for clinical upper gastrointestinal events in patients taking selective cyclooxygenase-2 inhibitors: A prospective, observational, cohort study in Taiwan.
BACKGROUND
Use of selective cyclooxygenase (COX)-2 inhibitors is associated with a better gastrointestinal (GI) safety profile than use of other NSAIDs. However, the risk factors for clinical upper GI events (symptomatic ulcers and ulcer complications) in COX-2 inhibitor users have been rarely evaluated in the past.


OBJECTIVE
The aim of this study was to assess the annual incidence of and identify the risk factors for clinical upper GI events in chronic COX-2 inhibitor (celecoxib and etoricoxib) users.


METHODS
A prospective, hospital-based, observational cohort study was conducted in patients taking COX-2 inhibitors (celecoxib or etoricoxib) without comorbidity. COX-2 inhibitor prescription was conducted according to the guidelines issued by the Taiwan National Health Insurance and was identified by the computerized prescribing system of the Taipei Veterans General Hospital, Taipei, Taiwan. Patients with cardiovascular disease, pulmonary, hepatic or renal insufficiency, or malignancy were excluded. Patients received regular follow-up once a month. Between visits, patients were asked to report to the outpatient clinic if they had persistent ulcer or GI symptoms (dyspepsia, vomiting, nausea, heartburn, or acid regurgitation) not relieved by antacids for 1 week, or to the emergency department if they had evidence of GI bleeding or ulcer complications (melena, hematemesis, hematochezia, or sudden onset of severe epigastric pain). Endoscopy was performed to document any gastroduodenal ulcers with or without ulcer complications. The primary end point was the annual incidence and the significant risk factors for clinical upper GI events (symptomatic ulcers and ulcer complications).


RESULTS
A total of 1158 COX-2 inhibitor users were identified; 96 refused to participate and 129 were excluded. The mean (SD) age of the remaining 933 COX-2 inhibitor users was 69 (15) years with 528 women (56.6%) and 405 men (43.4%). Mean time of follow-up was 12.4 months. The annual incidence of clinical upper GI events in these patients taking COX-2 inhibitors was 4.6% (44 events/959 patient-years), with symptomatic ulcers in 3.6% and ulcer complications in 1.0%. Multivariate logistic regression analysis found that a history of peptic ulcer disease (PUD) (odds ratio [OR = 4.61; 95% CI, 1.86-11.40; P = 0.001), concomitant use of steroids (OR = 2.99; 95% CI, 1.39-6.46; P = 0.005), aspirin (OR = 13.47; 95% CI, 5.89-30.82; P < 0.001), and other NSAIDs (OR = 60.49; 95% CI, 11.93-306.64; P < 0.001) were significant independent risk factors for clinical upper GI events in these patients taking COX-2 inhibitors. Age >60 years was not found to be a risk factor.


CONCLUSIONS
The annual incidence of clinical upper GI events was 4.6% in these Taiwanese patients without comorbidity taking COX-2 inhibitors. A history of PUD and concomitant use of steroids, aspirin, or other NSAIDs, were found to be significant risk factors for clinical upper GI events in these patients.
Hsiang
Kuo-Wei
KW
Department of Medicine, Taipei Veterans General Hospital, Taiwan, R.O.C.
Chen
Tseng-Shing
TS
Lin
Hsiao-Yi
HY
Luo
Jiing-Chyuan
JC
Lu
Ching-Liang
CL
Lin
Han-Chieh
HC
Lee
Kuei-Chuan
KC
Chang
Full-Young
FY
Lee
Shou-Dong
SD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D000068579:Celecoxib; D015331:Cohort Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects*; D000077613:Etoricoxib; D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010437:Peptic Ulcer / Q000150:complications; D011446:Prospective Studies; D011720:Pyrazoles / Q000009:adverse effects*; D011725:Pyridines / Q000009:adverse effects*; D012307:Risk Factors; D013449:Sulfonamides / Q000009:adverse effects*; D013450:Sulfones / Q000009:adverse effects*; D013624:Taiwan / Q000453:epidemiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D013449:Sulfonamides; D013450:Sulfones; D000068579:Celecoxib; D000077613:Etoricoxib