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Nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcers and gastrointestinal (GI) bleeding are important complications in patients requiring long-term NSAID therapy, particularly those with a previous history of peptic ulcers.
Proton pump inhibitor monotherapy remains a highly evidence-supported strategy for preventing NSAID-induced peptic ulcer recurrence and gastrointestinal bleeding in high-risk patients.
Nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcers and gastrointestinal (GI) bleeding are important complications in patients requiring long-term NSAID therapy, particularly those with a previous history of peptic ulcers. Several medications are used to minimize this risk, but the optimal strategy for NSAID ulcer prevention in high-risk patients remains uncertain. Hence, this study explored the efficacy and safety of various available preventive treatments.
This systematic review and network meta-analysis included 22 randomized controlled trials involving 7,768 patients using NSAIDs who had a documented history of peptic ulcers. The analysis compared proton pump inhibitors (PPIs), potassium-competitive acid blockers (P-CABs), cyclooxygenase-2 (COX-2) inhibitors, prostaglandin analogs, histamine-2 receptor antagonists (H2RAs), and gastric mucosal protective agents for the prevention of NSAID-related ulcer complications.
The primary efficacy outcomes were peptic ulcer recurrence and ulcer-related bleeding. Safety outcomes included treatment-emergent adverse events and discontinuation due to adverse events. Random-effects network models were used to assess relative and absolute risks, calculate numbers needed to treat (NNTs), and rank the preventive strategies.
Numerous treatment strategies demonstrated substantial protection against NSAID-induced peptic ulcer recurrence compared with placebo. COX-2 inhibitor plus PPI, P-CABs, COX-2 inhibitor monotherapy, and PPI monotherapy were associated with marked reductions in ulcer recurrence, with NNTs of 5–6.
A similar pattern was noted for the prevention of GI bleeding, suggesting that acid suppression and COX-2-selective strategies may provide clinically meaningful protection in high-risk NSAID users. However, safety findings differed between treatments. Prostaglandin analogs increased adverse events and treatment discontinuations, indicating poorer tolerability when compared with several alternative preventive approaches.
For high-risk NSAID users with a history of peptic ulcers, PPI monotherapy remains a well-supported approach for preventing recurrent peptic ulcers and GI bleeding. COX-2 inhibitor + PPI therapy and P-CABs may offer additional protection in very high-risk patients, but their use must be balanced against safety, tolerability, and cost considerations.
Digestive and Liver Disease
Comparing the efficacy and safety of medications to prevent nonsteroidal anti-inflammatory drug-induced ulcers in high-risk patients: A network meta-analysis
Xu Huang et al.
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