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

Rostom A, Muir K, Dube C, Lanas A, Jolicoeur E, Tugwell P - Drug Healthc Patient Saf (2009)

Bottom Line: 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.Acetylsalicylic acid appears to diminish the benefit of COX-2s over tNSAIDs.

View Article: PubMed Central - PubMed

Affiliation: University of Calgary, Calgary, Alberta, Canada;

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.

No MeSH data available.


Related in: MedlinePlus

Clinical ulcers (PUBs [perforation, obstruction, bleeding or the presence of a symptomatic ulcer]) with tNSAID + ASA vs tNSAID alone.Note: This is a non-randomized comparison.
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f13-dhps-1-047: Clinical ulcers (PUBs [perforation, obstruction, bleeding or the presence of a symptomatic ulcer]) with tNSAID + ASA vs tNSAID alone.Note: This is a non-randomized comparison.

Mentions: Five trials allowed assessment of the effects of the co-administration of ASA with a COX-2.65,82,91,114,116 In a pooled subgroup analysis of over 18,000 patients taking ASA, there was no statistically significant difference in the relative risk of ulcer complications (POBs) between those in the COX-2 arms and those in the non-selective arms of these trials (RR 0.93; 95% CI 0.68 to 1.27 for POBs). A small advantage of COX-2s over tNSAIDs cannot be ruled out by these results because this subgroup analysis might be under-powered The PUB analysis showed a statistically significant benefit for COX-2 + ASA vs tNSAID +ASA (RR 0.72; 95% CI 0.62 to 0.95), but data from one study could not be used in this analysis. In more than 40,000 patients in the COX-2 arms, patients taking ASA had a 3.46 (95% CI 2.44 to 4.91) greater relative risk of POBs than COX-2 users not taking ASA. Among 34,000 patients in the tNSAID arms of these studies, those taking ASA had a 1.65 greater relative risk of POBs than those not taking ASA, although this result did not reach statistical significance (95% CI 0.76 to 3.57). One must keep in mind that these are post-hoc subgroup analyses that might be subject to bias. Furthermore, the subgroup analysis within an tNSAID treatment group (eg, COX-2 vs COX-2 + ASA) represents a nonrandomized comparison in which differences could be influenced by factors other than ASA use (Figures 11 to 13).


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

Rostom A, Muir K, Dube C, Lanas A, Jolicoeur E, Tugwell P - Drug Healthc Patient Saf (2009)

Clinical ulcers (PUBs [perforation, obstruction, bleeding or the presence of a symptomatic ulcer]) with tNSAID + ASA vs tNSAID alone.Note: This is a non-randomized comparison.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108684&req=5

f13-dhps-1-047: Clinical ulcers (PUBs [perforation, obstruction, bleeding or the presence of a symptomatic ulcer]) with tNSAID + ASA vs tNSAID alone.Note: This is a non-randomized comparison.
Mentions: Five trials allowed assessment of the effects of the co-administration of ASA with a COX-2.65,82,91,114,116 In a pooled subgroup analysis of over 18,000 patients taking ASA, there was no statistically significant difference in the relative risk of ulcer complications (POBs) between those in the COX-2 arms and those in the non-selective arms of these trials (RR 0.93; 95% CI 0.68 to 1.27 for POBs). A small advantage of COX-2s over tNSAIDs cannot be ruled out by these results because this subgroup analysis might be under-powered The PUB analysis showed a statistically significant benefit for COX-2 + ASA vs tNSAID +ASA (RR 0.72; 95% CI 0.62 to 0.95), but data from one study could not be used in this analysis. In more than 40,000 patients in the COX-2 arms, patients taking ASA had a 3.46 (95% CI 2.44 to 4.91) greater relative risk of POBs than COX-2 users not taking ASA. Among 34,000 patients in the tNSAID arms of these studies, those taking ASA had a 1.65 greater relative risk of POBs than those not taking ASA, although this result did not reach statistical significance (95% CI 0.76 to 3.57). One must keep in mind that these are post-hoc subgroup analyses that might be subject to bias. Furthermore, the subgroup analysis within an tNSAID treatment group (eg, COX-2 vs COX-2 + ASA) represents a nonrandomized comparison in which differences could be influenced by factors other than ASA use (Figures 11 to 13).

Bottom Line: 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.Acetylsalicylic acid appears to diminish the benefit of COX-2s over tNSAIDs.

View Article: PubMed Central - PubMed

Affiliation: University of Calgary, Calgary, Alberta, Canada;

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.

No MeSH data available.


Related in: MedlinePlus