Prevention of NSAID-related upper gastrointestinal toxicity: a meta-analysis of traditional NSAIDs with gastroprotection and COX-2 inhibitors

Abstract

Background:Traditional NSAIDs (tNSAIDs) and COX-2 inhibitors (COX-2s) are important agents for the treatment of a variety or arthritic conditions. The purpose of this study was to systematically review the effectiveness of misoprostol, H2-receptor antagonists (H2RAs), and proton pump inhibitors (PPIs) for the prevention of tNSAID related upper gastrointestinal (GI) toxicity, and to review the upper gastrointestinal (GI) safety of COX-2s.Methods:An extensive literature search was performed to identify randomized controlled trials (RCTs) of prophylactic agents used for the prevention of upper GI toxicity, and RCTs that assessed the GI safety of the newer COX-2s. Meta-analysis was performed in accordance with accepted techniques.Results:39 gastroprotection and 69 COX-2 RCTs met inclusion criteria. Misoprostol, PPIs, and double doses of H2RAs are effective at reducing the risk of both endoscopic gastric and duodenal tNSAID-induced ulcers. Standard doses of H2RAs are not effective at reducing the risk of tNSAID-induced gastric ulcers, but reduce the risk of duodenal ulcers. Misoprostol is associated with greater adverse effects than the other agents, particularly at higher doses. COX-2s are associated with fewer endoscopic ulcers and clinically important ulcer complications, and have fewer treatment withdrawals due to GI symptoms than tNSAIDS. Acetylsalicylic acid appears to diminish the benefit of COX-2s over tNSAIDs. In high risk GI patients, tNSAID with a PPI or a COX-2 alone appear to offer similar GI safety, but a strategy of a COX-2 with a PPI appears to offer the greatest GI safety.Conclusion:Several strategies are available to reduce the risk of upper GI toxicity with tNSAIDs. The choice between these strategies needs to consider patients’ underlying GI and cardiovascular risk.

American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee

“…In this scenario, the TEP conditionally recommends the use of tramadol, duloxetine, or intraarticular hyaluronan injections. If the patient has a history of a symptomatic or complicated upper GI ulcer but has not had an upper GI bleed in the past year and the practitioner chooses to use an oral NSAID, the TEP strongly recommends using either a cyclooxygenase 2 (COX-2) selective inhibitor or a nonselective NSAID in combination with a proton-pump inhibitor; there was no preference expressed between these choices (29). In the clinical scenario where the above patient has had an upper GI bleed within the past year and the practitioner still chooses to use an oral NSAID, the TEP strongly recommends using a COX-2 selective inhibitor in combination with a proton-pump inhibitor.…”

1038 Cyclo-Oxygenase-2 Inhibitors or Nonselective NSAIDs Plus Gastroprotective Agents: What to Prescribe in Daily Clinical Practice?

“…46 Nevertheless, the preference for preventive strategies changed after warnings for an increased cardiovascular risk related to coxibs were released by regulatory agencies. 47 Although the risk of UGI complications with rofecoxib used to be higher than with celecoxib 48 , in a stratified analysis the estimate of nsNSAIDs plus GPAs compared to coxibs without rofecoxib after 2004 (i.e. celecoxib, etoricoxib, valdecoxib and lumiracoxib only) did not differ from the estimate including rofecoxib (before withdrawal).…”

Balancing cardiovascular and gastrointestinal risks in patients with osteoarthritis receiving nonsteroidal anti‑inflammatory drugs. A summary of guidelines from an international expert group

“…59 A meta-analysis also showed that the use of COX-2-selective inhibitors results in significantly lower rates of gastroduodenal ulcers and their complications than the use of ns-NSAIDs does. 60 As for the lower GI tract, the CONDOR trial showed that the proportion of patients with clinically significant events throughout the GI tract was significantly greater in patients taking diclofenac in combination with omeprazole than in those taking celecoxib.…”