Introduction
Non-variceal upper gastrointestinal bleeding (NVUGI) represents a significant gastrointestinal disorder with elevated mortality rates (1). Non-steroidal anti-inflammatory drugs (NSAIDs) have been firmly established as a risk factor for NVUGI, yet their precise impact on clinical outcomes remains insufficiently defined (2,3). Conversely, proton pump inhibitors (PPIs) have shown efficacy in reducing the incidence of NVUGI associated with NSAIDs. However, the extent of their influence on the clinical outcomes of NVUGI remains inadequately substantiated. Therefore, it is necessary to study the impact of these drugs on the clinical outcomes of patients with NVUGI.
Aims & Methods
The primary objective of our study is to compare the outcomes of NVUGI patients using NSAIDs with or without PPIs against those who did not use either medication. We conducted a retrospective analysis at a Spanish tertiary hospital, encompassing NVUGI cases from 2013 to 2022. NVUGI was defined as hematemesis or melena accompanied by a two-point decrease in hemoglobin or hemodynamic instability. Key clinical outcomes included the necessity for intervention (endoscopic, radiological, or surgical) and in-hospital mortality. Additionally, we compared baseline characteristics and pertinent clinical results such as rebleeding and delayed cardiovascular events. Statistical analysis was performed using SPSS.
Results
A total of 1200 cases were included, with 6.6% undergoing concomitant treatment with PPIs and NSAIDs, and 15.7% utilizing NSAIDs alone. Patients who took NSAIDs alone were younger (57 years vs. 66 in both other groups) and had a lower rate of comorbidities. Table 1 presents risk scores and outcome comparisons among the three groups. Statistical differences were observed, revealing lower acute mortality (9.6% vs. 7 vs. 2.8%, p=0.011) and reduced need for intervention (74% vs. 69.6 vs. 57.8%, p<0.001) in the group using NSAIDs alone. In multivariate analysis, MAP(ASH) > 2 (OR: 8, CI: 3-21, p<0.001) and ASA > 2 (OR: 4.4, CI: 1.7-11.4, p:0.002) emerged as independent risk factors for acute mortality, with an elevated MAP(ASH) score (OR: 8.8, CI: 5.9-13, p<0.001) being the sole independent factor explaining the need for intervention.
| | Naive | NSAIDs and PPIs | NSAIDs without PPIs | P |
| ASA 3-4 | 596 (64,3%) | 50 (63,3%) | 63 (33,7%) | <0,001 |
| MAPASH>2 | 448 (59,3%) | 39 (65%) | 52 (34,4) | <0,001 |
| Need for intervention | 691 (74%) | 55 (69,6%) | 108 (57,8%) | <0,001 |
| Rebleeding | 96 (10,3%) | 9 (11,4%) | 6 (3,2%) | 0,008 |
| Acute mortality | 86 (9,6%) | 5 (7%) | 5 (2,8%) | 0,011 |
| Mortality at 6 months | 77 (8,8%) | 7 (9,3%) | 7 (3,8%) | 0,075 |
| Delayed Cardiovascular event | 77 (8,7%) | 3 (3,9%) | 4 (2,2%) | 0,004 |
| Delayed rebleeding | 145 (16,4%) | 15 (19,5%) | 6 (3,3%) | <0,001 |
Conclusion
Patients abstaining from NSAIDs or those concurrently undergoing PPI therapy exhibited a higher incidence of intervention or acute mortality compared to those solely using NSAIDs. Through multivariate analysis, our study indicates that bleeding severity and baseline comorbidities, expressed by elevated MAP(ASH) scores and ASA classification, are pivotal factors influencing the clinical outcomes of NVUGI. In summary, the use of NSAIDs or PPIs to safeguard against gastrointestinal lesions induced by these drugs did not demonstrate a discernible impact on the short-term outcomes of patients with non-variceal upper gastrointestinal bleeding.
References
1. Lakatos L, Gonczi L, Lontai L, Izbeki F, Patai A, Racz I, et al. Incidence, predictive factors, clinical characteristics and outcome of non-variceal upper gastrointestinal bleeding – a prospective population-based study from hungary. Journal of Gastrointestinal and Liver Diseases. 2021 Sep 1;30(3):327–33.
2. Durak MB, Şimşek C, Yüksel İ. Clinical Outcomes of Older Patients with Non-Variceal Upper Gastrointestinal Bleeding Taking Anti-Thrombotic or Non-Steroidal Anti-Inflammatory Agents. Turkish Journal of Gastroenterology. 2023 Sep 1;34(9):918–24.
3. Åhsberg K, Höglund P, Kim WH, Von Holstein CS. Impact of aspirin, NSAIDs, warfarin, corticosteroids and SSRIs on the site and outcome of non-variceal upper and lower gastrointestinal bleeding. Scand J Gastroenterol. 2010 Dec;45(12):1404–15.