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Abstract
Despite decreasing Helicobacter pylori prevalence, the prevalence of peptic ulcer disease is increasing in the aged population, mainly due to increasing use of NSAIDs to manage pain and inflammation. In addition, low dose aspirin is employed as an anti-coagulant for those who have suffered or are at high risk of ischemic stroke and cardiovascular disease. However, NSAIDs and aspirin are injurious to mucosa of stomach and duodenum. NSAID-induced inhibition of mucosal prostaglandin synthesis is thought to be a major mechanism of gastrointestinal mucosal injury. The proportion of elderly has increased rapidly in Korea, with the proportion over 65 years old expected to be 24.3% in 2030. In this higher-risk population, the strategy to reduce the incidence of NSAID-related peptic ulcers and complications such as bleeding, obstruction and perforation is very important. Proton pump inhibitors (PPIs) with cyclooxygenase-2 inhibitor can be used for reducing the risk of NSAID-related ulcers and upper gastrointestinal (GI) complications. However, continuous use of PPI has several problems. In addition, NSAID-re-lated problems in the lower GI tract have increased, in contrast to the decrease of NSAID-related upper GI disease. The aim of this review is to provide an evidence-based knowledge regarding the mechanism, complications of treatment, and prevention strategies for NSAID- or aspirin-related peptic ulcer disease in Korea.
References
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Fig. 1.
Two related isoforms of the COX and LOX enzyme pathway and the role of non-steroidal anti-inflammatory drug (NSAID). COX-1 is expressed constitutively. It regulates normal cellular processes such as gastric cytoprotection, vascular homeostasis, platelet aggregation, and kidney function. COX-2 is increased during states of inflammation or in response to mitogenic stimuli. Nonselective NSAID inhibits the COX-1 and COX-2 pathways. Selective COX-2 NSAIDs inhibit only the COX-2 pathway. When COX-1 and COX-2 are inhibited, its inhibitor, 5-LOX enzyme, is more activated and LTB4, C4 and D4 are more induced. COX, cylcooxygenase; PG, prostaglan-din; TX, thromboxane; LOX, lipoxyge-nase; LT, leukotriene; GI, gastrointestinal.
Fig. 2.
Algorithm for long-term NSAID therapy according to a patient's gastrointestinal (GI) and cardiovascular (CV) risk factors. ASA, aspirin; ns-NSAID, non-specific NSAID; PPI, proton pump inhibitor. Adapted from the article of Scarpignato et al.81 (BMC Med 2015;13:55).
Table 1.
Changes of Clinical Characteristics of Patients with Peptic Ulcer in Korea
| Year | 199019 | 19956 | 199619 | 1996–199720 | 20006 | 2003–200818 | 20056 | 200619 | 200722 |
|---|---|---|---|---|---|---|---|---|---|
| Patient (n) | 60 | 1,518 | 80 | 180 | 1,980 | 475 | 2,042 | 61 | 310 |
| Age (yr), mean±SD | 47.8 | 50.8 | 53.8±13.7 | 58.2±14.9 | 58.1 | 61.5±15.0 | |||
| Aged patients (%) | 32.2 (≥60 yr) | 29.6 (>70 yr) | 48.1 (>65 yr) | ||||||
| NSAID and ulcerogenic drugs a (%) | 26.1 | 23.6 (NSAID),22.5 (aspirin) | 28.0 | 21.0 | |||||
| Helicobacter pylori infection (%) | 68.1 | 82.8 | 59.7 | 72.6 | 57.2 | 48.0 | |||
| Male (%) | 82.6 | 75.4 | 77.2 | 70.3 | 66.7 | 66.7 | |||
| Location of ulcer | |||||||||
| Gastric ulcer (%) | 52.4 | 53.3 | 57.3 | 59.1 | 56.0 | 56.0 | 52.0 | 61.2 | |
| Duodenal ulcer (%) | 40.4 | 46.7 | 44.4 | 40.9 | 44.0 | 44.0 | 40.7 | 38.8 | |
| Smoking (%) | 58.9 | 34.3 | |||||||
| Alcohol (%) | 43.9 | 35.8 | |||||||
| Bleeding (%) | 17.8 | 35.5 |
Table 2.
Demographic Characteristics of Korean Patients with Peptic Ulcer Bleeding and Perforated Peptic Ulcer in 2006–20077,8
| Variable |
Peptic ulcer bleeding (n=21,107)7 |
Perforated peptic ulcer (n=4,258)8 |
||||
|---|---|---|---|---|---|---|
| n (%) | 30-day mortality No. of deaths (%) | Crude MRR (95% CI) | n (%) | 30-day mortality No. of deaths (%) | Crude MRR (95% CI) | |
| Total | 21,107 (100) | 454 (2.2) | 4,258 | 135 (3.2) | ||
| Age (yr) | ||||||
| <60 | 11,099 (52.6) | 92 (0.8) | 1.00 | 3,143 (73.8) | 33 (1.1) | 1.00 |
| 60–79 | 8,453 (40.0) | 243 (2.9) | 3.50 (2.75–4.45) | 892 (20.9) | 59 (6.6) | 2.76 (1.7–4.5) |
| ≥80 | 1,555 (7.4) | 119 (7.7) | 9.55 (7.28–12.5) | 223 (5.2) | 43 (19.3) | 8.39 (4.8–14.1) |
| Sex | ||||||
| Male | 16,177 (76.6) | 296 (1.8) | 1.00 | 3,650 (85.7) | 74 (2.0) | 1.00 |
| Female | 4,930 (23.4) | 158 (3.2) | 1.78 (1.46–2.16) | 608 (14.3) | 61 (10.0) | 1.71 (1.1–2.6) |
| Charlson comorbidity index | ||||||
| Low (0) | 19,779 (93.7) | 366 (1.9) | 1.00 | 3,291 (77.3) | 38 (1.2) | 1.00 |
| Medium (1–2) | 1,158 (5.5) | 64 (5.5) | 3.53 (2.75–4.53) | 747 (17.5) | 60 (8.0) | 3.85 (2.5–6.0) |
| High (≥3) | 170 (0.8) | 14 (8.2) | 4.62 (2.71–7.88) | 220 (5.2) | 37 (16.8) | 8.52 (5.1–14.3) |
| PU-related hospitalization | ||||||
| No | 20,230 (95.8) | 427 (2.1) | 1.00 | 4,053 (95.2) | 118 (2.9) | Excluded c |
| Yes | 877 (4.2) | 27 (3.1) | 1.47 (0.99–2.19) | 205 (4.8) | 17 (8.3) | |
| Ulcer-related drug a users | ||||||
| No | 15,605 (73.9) | 301 (1.9) | 1.00 | 2,710 (63.6) | 43 (1.6) | Excluded c |
| Yes | 5,502 (26.1) | 153 (2.8) | 1.45 (1.19–1.77) | 1,548 (36.4) | 92 (5.9) | |
| Antiulcer drug b users | ||||||
| No | 8,294 (39.3) | (1.9) d | 1.00 | 3,602 (84.6) | 134 (3.7) | Excluded c |
| Yes | 12,813 (60.7) | (2.8) d | 1.45 (1.19–1.77) | 656 (15.4) | 1 (0.2) | |
MRR, mortality rate ratio; PU, peptic ulcer; PUB, peptic ulcer bleeding; PPU, perforated peptic ulcer.
a Ulcer-related drug is defined as NSAIDs (including aspirin and COX-2 inhibitors), oral glucocorticoids, and anticoagulant (warfarin and clopidogrel).
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