The association between
This case-control study investigated 340 patients with PUB between 2012 and 2016. The control group comprised age and sex-matched patients with endoscopically documented non-bleeding ulcers. Using logistic regression analysis, the adjusted odds ratio (AOR) was calculated for the risk of PUB.
Of the patients investigated, 57.9% in the study group and 51.8% in the control group were diagnosed with
Both NSAIDs and aspirin are independent risk factors for bleeding in patients with PUD. Additionally, low-dose aspirin therapy concomitant with
In a systematic review, the pooled relative risk (RR) for NSAIDs-related gastrointestinal (GI) bleeding was 4.50 (95% confidence interval [CI]: 3.82∼5.31) and the RR of aspirin-related GI bleeding was 2.07 (95% CI: 1.61∼2.66) [
In daily clinical practice, the concomitant use of NSAIDs or aspirin in
The risk of bleeding in PUD subjects with
This was a hospital-based case-control study performed at the Kangdong Sacred Heart Hospital (IRB no. 2017-12-011-001). We recruited consecutive patients with PUB admitted to our institution from 2012 to 2016. The study group was PUB patients who complained of melena or hematemesis at admission and underwent endoscopy within 24 hours of admission. The control group was patients with an endoscopic diagnosis of PUD without bleeding and was matched for age and sex with the PUB group. PUD was defined as a mucosal break, at least 5 mm in diameter, with visible depth assessed by an endoscopist. In most patients, biopsy specimens were taken from the edge of the ulcer to exclude malignancy in the gastric ulcer.
In the PUB group, exclusion criteria were as follows: (1) patients who had bleeding from areas other than the peptic ulcer such as gastric or esophageal varices, upper GI malignancy, angiodysplasia, Mallory–Weiss syndrome; (2) patients who had taken antibiotics or proton pump inhibitor (PPI) within the last one month of enrollment; (3) patients with coagulopathy; (4) patients with liver cirrhosis; and (5) patients who had a history of PUB.
The PUD group comprised age (±5 years) and sex-matched, non-bleeding ulcer patients who visited the outpatient unit during the same period as that of the PUB patients. In the PUD group, subjects who had taken antibiotics or PPI within the last one month of enrollment. To exclude patients with ulcer bleeding, patients with active-stage ulcer on endoscopy were excluded in PUD group. We reviewed medical records and collected clinical information such as drug history, smoking, alcohol history, and underlying disease. Current NSAIDs or aspirin use was defined as at least one dose taken within 4 weeks before the index date of endoscopic procedure. Low-dose aspirin was defined as a dose no greater than 300 mg/day. In antiplatelet agents, clopidogrel was included in 95% of total patients and only warfarin other than direct oral anticoagulant was included. We defined the patients who were presently smoking as ‘smokers’ and the patients who consumed more than 40 g of alcohol a day in men and over than 20 g a day in women as ‘alcoholics.’
All data were analyzed using SPSS software for Windows, version 19.0 (IBM Corp., Armonk, NY, USA). Univariate and multivariate analysis were performed to compare clinical features between the PUB and PUD groups using the chi-square test or Fisher’s exact test for categorical variables and independent sample t-test for continuous variables. Conditional logistic-adjusted regression analyses were carried out to compute RRs and 95% CI, similar to that in a recent study [
In all, 680 patients were enrolled in this study. The median age of patients was 58 (range: 19∼88) years and 74.4% of patients were male.
To evaluate independent risk factors for bleeding in subjects with PUD, we conducted a logistical regression analysis. On multivariate analysis, low-dose aspirin (adjusted odds ratio [AOR] 3.92,
In the present case-control study, we investigated the interaction between
Until now, there have been several studies exploring the synergistic effect of NSAIDs or aspirin with
In contrast, Okan et al. [
Our study showed no synergistic interaction between NSAIDs and
There are few literatures about the interaction between aspirin and
Most guidelines recommend that
On multivariate analysis, NSAIDs and aspirin were independent risk factors for bleeding, in patients with PUD. The result was concordant with results from previous studies [
Additionally, in our PUB population, the proportion of GU was higher than duodenal ulcers (DU) (68.5% vs. 30.9%) and the proportion of DU was quite lower than that in previous studies (30.9% vs. 40~59%) [
This study has some limitations. First, it was a retrospective study; therefore, it might have a potential bias. To minimize the bias, the PUD group was selected from patients who were diagnosed with PUD during the same period as those in the PUB group and consecutively enrolled. Second, there might be a recall bias about the drug exposure history especially in the PUD group since they visited the outpatient units. This could have resulted in an underestimated proportion of drug intake in the PUD group and we could not identify exact drug dose or duration. Third, as mentioned above, we could not perform secondary method for
In conclusion, both NSAIDs and aspirin are independent risk factors for bleeding in patients with PUD and synergistic interaction was observed between
No potential conflict of interest relevant to this article was reported.
Comparison of Clinical Characteristics between PUB and PUD Groups
Characteristic | PUB group (n=340) | PUD group (n=340) | |
---|---|---|---|
Age | 58.7±13.5 | 58.3±13.7 | 0.686 |
Male | 253 (74.4) | 253 (74.4) | <1.000 |
197 (57.9) | 176 (51.8) | 0.106 | |
Aspirin | 116 (34.1) | 38 (11.2) | <0.001 |
NSAID | 54 (15.9) | 21 (6.2) | <0.001 |
Antiplatelet agent | 27 (7.9) | 15 (4.4) | 0.056 |
Warfarin | 17 (5.0) | 1 (0.3) | <0.001 |
Smoking | 133/338 (39.3) | 59/238 (24.8) | <0.001 |
Alcohol | 138/339 (40.7) | 75/238 (31.5) | 0.024 |
Ulcer location | <0.001 | ||
GU | 233 (68.5) | 156 (45.9) | |
DU | 105 (30.9) | 158 (46.5) | |
GU+DU | 2 (0.6) | 26 (7.6) |
Values are presented as mean±standard deviation, number (%), or number/total number (%).
PUB, peptic ulcer bleeding; PUD, peptic ulcer disease; NSAID, non-steroidal anti-inflammatory drugs; GU, gastric ulcer; DU, duodenal ulcer.
Relative Risk (RR) for Bleeding Associated with Drugs and
Factor | RR (95% CI) | PUB group (n=340) | PUD group (n=340) |
---|---|---|---|
No NSAID-No |
1 | 109 | 154 |
NSAID-No |
4.8 (2.3∼10.1) | 34 | 10 |
No NSAID- |
1.5 (1.1∼2.1) | 177 | 165 |
NSAID- |
2.9 (1.3∼6.8) | 19 | 9 |
NSAID-ASA- |
0.7 (0.1∼7.9) | 1 | 2 |
No ASA-No |
1 | 85 | 143 |
ASA-No |
4.6 (2.6∼8.2) | 58 | 21 |
No ASA- |
1.4 (1.0∼2.1) | 139 | 159 |
ASA- |
6.3 (3.4∼11.9) | 57 | 15 |
NSAID-ASA- |
0.8 (0.1∼9.4) | 1 | 2 |
PUB, peptic ulcer bleeding; PUD, peptic ulcer disease; NSAID, non-steroidal anti-inflammatory drugs; ASA, aspirin.
Multivariate Analysis for the Risk Factors of Bleeding Compared with Non-Bleeding Peptic Ulcer Disease
Risk factor | Adjusted odds ratio (95% confidence interval) | |
---|---|---|
1.41 (0.97∼2.07) | 0.076 | |
Aspirin | 3.92 (2.39∼6.46) | <0.001 |
NSAID | 2.98 (1.61∼5.54) | 0.001 |
Warfarin | 14.57 (1.86∼114.06) | 0.011 |
Ulcer location (GU |
1.65 (1.13∼2.41) | 0.01 |
Smoking | 1.97 (1.25∼3.09) | 0.004 |
Alcohol | 1.21 (0.78∼1.87) | 0.389 |
NSAID, non-steroidal anti-inflammatory drugs; GU, gastric ulcer; DU, duodenal ulcer.