Introduction
In the context of proper proton pump inhibitors (PPI) use, over-prescription is commonly criticized. Conversely, few studies have assessed the consequences of not prescribing PPIs in patients with a recognized indication for prophylactic treatment. This study aims to compare, in a cohort of patients with upper gastrointestinal bleeding (UGB), those with and without PPI at bleeding onset and in particular patients who are considered at high risk for UGB.
Aims & Methods
We undertook a post-hoc analysis of data from a prospective multicenter observational study (1) conducted in 46 French medical centers, which included all consecutive UGB cases that occurred between November 2017 and October 2018. Data about patients’ demographics, clinical, endoscopic and prognostic features were collected. First, we explored bleeding etiology in patients with and without PPI at the time of bleeding. Then, we calculated the rate of prophylactic PPI prescription in patients having an UGB related to peptic ulcer disease (PUD) and notably in those considered at higher risk of bleeding according to international guidelines (2, 3). In patients who had peptic ulcer bleeding, we compared those with and without PPI upon bleeding onset, in terms of baseline demographics and bleeding severity. We then analyzed the predictors of severe UGB defined by a Glasgow Blatchford score (GBS)≥11. We included PPI prophylaxis in our analysis to determine its role in reducing bleeding severity.
Results
A total of 2,498 patients with UGB were included, of whom 777 (31%) were on PPI at the time of bleeding. UGB related to PUD was significantly less prevalent in patients with PPI than in those without PPI (28% vs 46%, respectively; p< 0.0001). No difference was observed in the frequency of bleeding related to portal hypertension nor to esophagitis between the two groups (P=0.64 and 0.26, respectively) whereas hemorrhagic angiodysplasias were more common in the group with PPI (p<0.0001).
Of the 893 patients who had UGB related to PUD, only 21.5% were on PPI. These patients, compared to those without PPI, were older (74 vs 69 years; p<0.0001) and had more comorbidities (defined by a Charlson score≥3) (p<0.0001), notably at cardiovascular level. Ulcer was more likely to be located in the stomach in patients with PPI and in the duodenum in those without PPI (p=0.002). Helicobacter Pylori prevalence and Forrest classification were comparable in both groups (p=0.11 and 0.18, respectively). There was no statistically significant difference in terms of severity measured by mean GBS, blood transfusions or 6-week mortality and rebleeding rates (p>0.05).
In patients at high risk for UGB, we noted an under-prescription of PPI prophylaxis (Table 1). Independent predictors for severe bleeding according to multivariate analysis were the following: age≥65years (p=0.001), in-hospital bleeding (p=0.012), Charlson score≥3 (p<0.0001) and dual anti-platelets use (p=0.031). The absence of PPI prophylaxis did not affect bleeding severity (p=0.5).
| Table 1: PPI prescription rates in high risk patients*: |
| PUD-related UGB | High Risk patients | PPI-prescription rate |
| NSAIDS | 112 | 74 | 20% |
| AP | 312 | 122 | 35% |
| OAC | 178 | 89 | 34% |
| Dual-AP | 46 | 16 | 50% |
| OAC+AP | 50 | 7 | 29% |
| NSAIDS: non-steroidal anti-inflammatory drugs, AP: anti-platelets, OAC: oral anti-coagulants, PUD: peptic ulcer disease, UGB: upper gastrointestinal bleeding, PPI: proton pump inhibitor, * Risk stratification according to European Society of Cardiologist (2) and American college of Gastroenterology guidelines (3). |
Conclusion
In this cohort of patients with UGB, peptic ulcer bleeding occurred less frequently in patients on PPI. However, PPI treatment did not affect bleeding severity which was mainly determined by patients’ age and comorbidities. Most importantly, we noted a significant under-prescription of prophylactic PPI in high-risk groups having a well-recognized indication for gastric protection. This finding must be highlighted when discussing proper prescribing practices.
References
(1) Quentin V, Remy AJ, Macaigne G et al. Prognostic factors associated with upper gastrointestinal bleeding based on the French multicenter SANGHRIA trial. Endosc Int Open 2021; 09: E1504–E1511 DOI 10.1055/a-1508-5871
(2) Marco Roffi etal. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation, European Heart Journal (2016) 37, 267–31
(3) Lanza FL, Chan FKL, Quigley EMM. Practice Parameters Committee of the American College of Gastroenterology. Guidelines for prevention of NSAID-related ulcer com- plications. Am J Gastroenterol 2009;104:728–738.
Disclosure
No conflict of interest to disclose in relation to this work