Vol 44 # 4 December 2012 - Kma.org.kw

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KUWAIT MEDICAL JOURNAL
December 2012
Letter to the Editor
Individual Cyclooxygenase-2 Inhibitors on the Risk of
Peptic Ulcer Disease: A Population-Based Cohort in Taiwan
Shih-Wei Lai 1,2 , Kuan-Fu Liao 3-5 , Hsueh-Chou Lai 6,7 , Chih-Hsin Muo 8,9 , Fung-Chang Sung 8,9 , Pei-Chun Chen 10
1
School of Medicine, 3 Graduate Institute of Integrated Medicine, 6 School of Chinese Medicine, and
8
Department of Public Health, China Medical University, Taichung, Taiwan
2
Department of Family Medicine, 7 Department of Internal Medicine, 9 Management Office for Health Data,
China Medical University Hospital, Taichung, Taiwan
4
Department of Internal Medicine, Taichung Tzu Chi General Hospital, Taichung, Taiwan
5
Department of Health Care Administration, Central Taiwan University of Science and Technology, Taichung, Taiwan
10
Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University ,
Taipei, Taiwan
Kuwait Medical Journal 2012; 44 (4): 347 - 348
To date, little evidence is available about the
association between peptic ulcer disease and
commercially available cyclooxygenase-2 inhibitors
(COX-2 inhibitors) in Taiwan. Therefore, we conducted
this population-based cohort study from the National
Health Insurance (NHI) program in Taiwan to directly
compare the effects of individual COX-2 inhibitors on
the risk of peptic ulcer disease. The details of insurance
program can be found in previous studies [1-4] . This
study consisted of 1388 patients aged 20 years or older
who had ever used COX-2 inhibitors (770 men and
618 women, mean age 51.4 years, standard deviation
18.5 years), and 5403 subjects who never used COX-
2 inhibitors (3080 men and 2323 women, mean age
50.6 years, standard deviation 18.2 years), frequency
matched with sex, age, and index year for comparison,
from 2000 to 2006. The incidence of peptic ulcer disease
(based on International Classification of Diseases
9th Revision - Clinical Modification, ICD-9 531, 532,
533, and 534) at the end of 2009 was determined. An
index date for patients with peptic ulcer disease was
defined as their date of diagnosis. Subjects diagnosed
with peptic ulcer disease before the index date were
excluded from the study. The subjects, who had ever
used combination of COX-2 inhibitors, or ever used
aspirin, or other non-steroidal anti-inflammatory
drugs (NSAIDs), were excluded from this study. Other
co-morbidities before the index date were defined as
follows: Helicobacter pylori infection (ICD-9 041.86),
tobacco use (ICD-9 305.1), and alcoholism (ICD-9 303,
305.00, 305.01, 305.02, 305.03 and V11.3, and A-code
A215). The potentially related medications included
were as follows: proton pump inhibitor, histamine-2
receptor antagonist, clopidogrel, ticlopidine, systemic
corticosteroid, warfarin, and heparin.
We found that the incidence of peptic ulcer disease
was 3.26-fold higher in the COX-2 inhibitors group,
compared with the non-COX-2 inhibitors group
(19.28 per 1000 person-years Vs 5.91 per 1000 personyears,
95% confidence interval - CI = 2.63 - 4.04). After
controlling for variables that were significantly related
to COX-2 inhibitors found in the Chi-square test, the
multivariable Cox proportional hazard regression
showed use of COX-2 inhibitors was substantially
associated with increased risk of peptic ulcer disease
(hazard ratio - HR = 3.23, 95% CI = 2.59 - 4.04). In
sub-analysis, individual COX-2 inhibitors, including
celecoxib (HR = 3.29, 95%CI = 2.00 - 5.39), meloxicam
(HR = 3.19, 95%CI = 2.33 - 4.36), nabumetone (HR =
3.19, 95% CI = 2.39 - 4.25), and nimesulide (HR = 2.21,
95% CI = 1.08-4.52), would substantially increase the
risk of peptic ulcer disease, respectively.
Previous studies have reported that COX-2
inhibitors can reduce the risk of upper gastrointestinal
ulcers, compared with non-selective NSAIDs [5, 6] . In
Rostom et al’s systematic review [7] , COX-2 inhibitors
correlate with lower risk of upper gastrointestinal
ulcers (relative risk, 0.26 - 0.39), compared with
non-selective NSAIDs. An observational study by
Hsiang et al in Taiwan [8] , the annual incidence of
Address correspondence to:
Pei-Chun Chen, Ph.D., MSPH, Projected-appointed Assistant Professor, Graduate of Epidemiology and Preventive Medicine, National Taiwan University
College of Public Health, No.17, Xu-Zhou Road, Taipei, 10020, Taiwan. Tel: 886-2-33668021, E-mail: eliz0118@gmail.com