Combining COX-2 inhibitors with PPIs may provide the best gastrointestinal protection to prevent NSAID-associated GI toxicity, study authors concluded in a meta-analysis published in Alimentary Pharmacology & Therapeutics

Non-steroidal anti-inflammatory drugs (NSAIDs) are generally safe analgesics but they may increase the risk of developing stomach and intestinal ulcers.  With many strategies to prevent NSAID-associated gastrointestinal (GI) toxicity, Professor Jin Ling Tang and study coauthors aimed to evaluate the comparative effectiveness of various clinical strategies.

They searched for randomized controlled trials comparing the risk of GI adverse effects in patients taking nonselective NSAIDs, selective cyclooxygenase (COX)-2 inhibitors, or nonselective NSAIDs/COX-2 inhibitors + GI protective agents (eg, proton pump inhibitors [PPIs], histamine-2 receptor antagonists, misoprostol). Researchers performed both pairwise meta-analysis and Bayesian network meta-analysis. 

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A total of 82 trials including 125,053 patients were included. The analysis showed that significantly lower risk of clinical GI events was associated with selective COX-2 inhibitors + PPIs (ulcer complications risk ratio [RR] 0.07, 95% CrI: 0.02–0.18), selective COX-2 inhibitors (ulcer complications RR 0.25, 95% CrI: 0.15–0.38; symptomatic ulcer RR 0.12, 95% CrI: 0.04–0.30), nonselective NSAIDs + PPIs (ulcer complications RR 0.28, 95% CrI: 0.18–0.41; symptomatic ulcer RR 0.11, 95% CrI: 0.04–0.23), nonselective NSAIDs + misoprostol (ulcer complications RR 0.47, 95% CrI: 0.24–0.81; symptomatic ulcer RR 0.41, 95% CrI: 0.13–1.00) compared with nonselective NSAIDs. 

Overall, selective COX-2 inhibitors + PPIs were associated with the lowest absolute event probability and highest rank for all efficacy endpoints, followed by selective COX-2 inhibitors and nonselective NSAIDs + PPIs

Professor Tang concluded that combining COX-2 inhibitors + PPIs offered the best GI protection. Although this combination is not recommended for all patients who require an NSAID, “it is the safest and most effective treatment strategy for those at high risk of ulcer bleeding from NSAID treatment.”

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