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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

Misoprostol vs placebo for the prevention of gastric ulcers – efficacy by dose.
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f1-dhps-1-047: Misoprostol vs placebo for the prevention of gastric ulcers – efficacy by dose.

Mentions: All the studied doses of misoprostol significantly reduced the risk of endoscopic ulcers, and a dose response relationship was demonstrated for endoscopic gastric ulcers. Six studies with 2,461 patients used misoprostol 400 μg.22,25,30,33,36,42 1 study with 928 patients used 600 μg daily,36 and 7 with 2,423 patients used 800 μg daily.21,29–32,36,38 Misoprostol 800 μg daily was associated with the lowest risk (RR 0.17; 95% CI 0.11 to 0.24) of endoscopic gastric ulcers when compared to placebo, whereas misoprostol 400 ug daily was associated with a relative risk of 0.42 (95% CI 0.28 to 0.67, random effects model for heterogeneity) (Figure 1). This difference between high- and low-dose misoprostol reached statistical significance (P0.0055). The intermediate misoprostol dose (600 μg daily) was not statistically different from either the low or high dose. The pooled relative risk reduction of 78% (4.7% absolute risk difference, RR 0.21; 95% CI 0.09 to 0.49) for duodenal ulcers with misoprostol 800 μg daily was not statistically different from those of the lower daily misoprostol dosages.


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)

Misoprostol vs placebo for the prevention of gastric ulcers – efficacy by dose.
© Copyright Policy
Related In: Results  -  Collection

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

f1-dhps-1-047: Misoprostol vs placebo for the prevention of gastric ulcers – efficacy by dose.
Mentions: All the studied doses of misoprostol significantly reduced the risk of endoscopic ulcers, and a dose response relationship was demonstrated for endoscopic gastric ulcers. Six studies with 2,461 patients used misoprostol 400 μg.22,25,30,33,36,42 1 study with 928 patients used 600 μg daily,36 and 7 with 2,423 patients used 800 μg daily.21,29–32,36,38 Misoprostol 800 μg daily was associated with the lowest risk (RR 0.17; 95% CI 0.11 to 0.24) of endoscopic gastric ulcers when compared to placebo, whereas misoprostol 400 ug daily was associated with a relative risk of 0.42 (95% CI 0.28 to 0.67, random effects model for heterogeneity) (Figure 1). This difference between high- and low-dose misoprostol reached statistical significance (P0.0055). The intermediate misoprostol dose (600 μg daily) was not statistically different from either the low or high dose. The pooled relative risk reduction of 78% (4.7% absolute risk difference, RR 0.21; 95% CI 0.09 to 0.49) for duodenal ulcers with misoprostol 800 μg daily was not statistically different from those of the lower daily misoprostol dosages.

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