Context: Helicobacter pylori infection and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are the primary etiological factors contributing to gastric ulcer disease, characterized by mucosal erosions in the stomach. This condition remains a significant global health challenge, particularly in low- and middle-income countries, where it substantially contributes to morbidity and premature mortality. Complications such as gastrointestinal bleeding and perforation exacerbate the disease burden, underscoring the need for effective preventive and therapeutic strategies. Objectives: To evaluate the effectiveness of proton pump inhibitors, prostaglandin analogues, and histamine-2 (H2) receptor antagonists in preventing and healing gastric ulcers caused by H. pylori and NSAID use. The study aims to identify optimal treatments and explore patient-specific responses for improved, personalized therapy. Methods: This systematic review and meta-analysis evaluated the efficacy of gastroprotective treatments, including proton pump inhibitors (PPIs), prostaglandin analogues, and histamine-2 receptor antagonists (H2RAs), in preventing and healing gastric ulcers. A comprehensive search was conducted across PubMed, Embase, and the Cochrane Library. Inclusion criteria focused on Randomized Controlled Trials (RCTs) assessing these treatments in patients with gastric ulcers. Quality assessment was performed using the adapted Newcastle–Ottawa Scale. The DerSimonian and Laird random-effects model was employed to determine pooled effect sizes, with heterogeneity assessed using Cochran’s Q and I² statistics. All analyses were conducted using Stata/MP 17.0. Results: The search identified 2,687 records, with 116 studies meeting the inclusion criteria after rigorous screening and quality assessment. The meta-analysis included studies on PPIs, prostaglandin analogues, and H2RAs, involving 18,042 participants in the treatment groups and 13,255 in the control groups. PPIs significantly reduced the incidence of gastric ulcers (log odds ratio = -1.17, 95% CI: -1.97 to -0.37, P < 0.001) with high heterogeneity (I² = 98.13%). Prostaglandin analogues (log odds ratio = -1.61, 95% CI: -2.49 to -0.73, P < 0.001) and H2RAs (log odds ratio = -0.86, 95% CI: -1.92 to 0.20, P < 0.001) also demonstrated significant protective effects despite high heterogeneity. Conclusions: Gastroprotective treatments, particularly PPIs and prostaglandin analogues, are effective in reducing gastric ulcer incidence. The high heterogeneity among studies suggests the need for individualized treatment approaches. Further research is warranted to refine protocols and optimize patient-specific therapies.
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