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Prevention of chronic NSAID induced upper gastrointestinal toxicity.

Abstract

BACKGROUND

Non-steroidal anti-inflammatory drugs (NSAIDs) are important agents in the management of arthritic and inflammatory conditions, and are among the most frequently prescribed medications in North America and Europe. However, there is overwhelming evidence linking these agents to a variety of gastrointestinal (GI) toxicities.

OBJECTIVES

To review the effectiveness of common interventions for the prevention of NSAID induced upper GI toxicity.

SEARCH STRATEGY

A literature search was conducted, according to the Cochrane methodology for identification of randomized controlled trials in electronic databases, including MEDLINE from 1966 to January 2000, Current Contents for 6 months prior to January 2000, Embase to Febuary 1999, and a search of the Cochrane Controlled Trials Register from 1973 to 1999. Recent conference proceedings were reviewed and content experts and companies were contacted.

SELECTION CRITERIA

Randomized controlled clinical trials (RCTs) of prostaglandin analogues (PA), H2-receptor antagonists (H2RA) or proton pump inhibitors (PPI) for the prevention of chronic NSAID induced upper GI toxicity were included.

DATA COLLECTION AND ANALYSIS

Two independent reviewers extracted data regarding population characteristics, study design, methodological quality and number of patients with endoscopic ulcers, ulcer complications, symptoms, overall drop-outs, drop outs due to symptoms. Dichotomous data was pooled using Revman V3.1. Heterogeneity was evaluated using a chi square test.

MAIN RESULTS

Thirty-three RCTs met the inclusion criteria. All doses of misoprostol significantly reduced the risk of endoscopic ulcers. Misoprostol 800 ug/day was superior to 400 ug/day for the prevention of endoscopic gastric ulcers (RR=0.18, and RR=0. 38 respectively, p=0.0055). A dose response relationship was not seen with duodenal ulcers. Misoprostol caused diarrhea at all doses, although significantly more at 800ug/day than 400ug/day (p=0.0012). Misoprostol was the only prophylactic agent documented to reduce ulcer complications. Standard doses of H2RAs were effective at reducing the risk of endoscopic duodenal (RR=0.24; 95% CI: 0.10-0. 57) but not gastric ulcers(RR=0.73; 95% CI:0.50-1.09). Both double dose H2RAs and PPIs were effective at reducing the risk of endoscopic duodenal and gastric ulcers (RR=0.44; 95% CI:0.26-0.74 and RR=0.37;95% CI;0.27-0.51 respectively for gastric ulcer), and were better tolerated than misoprostol.

REVIEWER'S CONCLUSIONS

Misoprostol, PPIs, and double dose H2RAs are effective at preventing chronic NSAID related endoscopic gastric and duodenal ulcers. Lower doses of misoprostol are less effective and are still associated with diarrhea. Only Misoprostol 800ug/day has been directly shown to reduce the risk of ulcer complications.

Authors+Show Affiliations

University of Ottawa Department of Medicine, A1 - Endoscopy Unit, Ottawa Hospital - Civic Campus, 1053 Carling Ave., Ottawa, Ontario, Canada, K1Y-4E9. alrostom@cyberus.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review
Systematic Review

Language

eng

PubMed ID

10908548

Citation

Rostom, A, et al. "Prevention of Chronic NSAID Induced Upper Gastrointestinal Toxicity." The Cochrane Database of Systematic Reviews, 2000, p. CD002296.
Rostom A, Wells G, Tugwell P, et al. Prevention of chronic NSAID induced upper gastrointestinal toxicity. Cochrane Database Syst Rev. 2000.
Rostom, A., Wells, G., Tugwell, P., Welch, V., Dube, C., & McGowan, J. (2000). Prevention of chronic NSAID induced upper gastrointestinal toxicity. The Cochrane Database of Systematic Reviews, (3), CD002296.
Rostom A, et al. Prevention of Chronic NSAID Induced Upper Gastrointestinal Toxicity. Cochrane Database Syst Rev. 2000;(3)CD002296. PubMed PMID: 10908548.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prevention of chronic NSAID induced upper gastrointestinal toxicity. AU - Rostom,A, AU - Wells,G, AU - Tugwell,P, AU - Welch,V, AU - Dube,C, AU - McGowan,J, PY - 2000/7/25/pubmed PY - 2001/7/6/medline PY - 2000/7/25/entrez SP - CD002296 EP - CD002296 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 3 N2 - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are important agents in the management of arthritic and inflammatory conditions, and are among the most frequently prescribed medications in North America and Europe. However, there is overwhelming evidence linking these agents to a variety of gastrointestinal (GI) toxicities. OBJECTIVES: To review the effectiveness of common interventions for the prevention of NSAID induced upper GI toxicity. SEARCH STRATEGY: A literature search was conducted, according to the Cochrane methodology for identification of randomized controlled trials in electronic databases, including MEDLINE from 1966 to January 2000, Current Contents for 6 months prior to January 2000, Embase to Febuary 1999, and a search of the Cochrane Controlled Trials Register from 1973 to 1999. Recent conference proceedings were reviewed and content experts and companies were contacted. SELECTION CRITERIA: Randomized controlled clinical trials (RCTs) of prostaglandin analogues (PA), H2-receptor antagonists (H2RA) or proton pump inhibitors (PPI) for the prevention of chronic NSAID induced upper GI toxicity were included. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data regarding population characteristics, study design, methodological quality and number of patients with endoscopic ulcers, ulcer complications, symptoms, overall drop-outs, drop outs due to symptoms. Dichotomous data was pooled using Revman V3.1. Heterogeneity was evaluated using a chi square test. MAIN RESULTS: Thirty-three RCTs met the inclusion criteria. All doses of misoprostol significantly reduced the risk of endoscopic ulcers. Misoprostol 800 ug/day was superior to 400 ug/day for the prevention of endoscopic gastric ulcers (RR=0.18, and RR=0. 38 respectively, p=0.0055). A dose response relationship was not seen with duodenal ulcers. Misoprostol caused diarrhea at all doses, although significantly more at 800ug/day than 400ug/day (p=0.0012). Misoprostol was the only prophylactic agent documented to reduce ulcer complications. Standard doses of H2RAs were effective at reducing the risk of endoscopic duodenal (RR=0.24; 95% CI: 0.10-0. 57) but not gastric ulcers(RR=0.73; 95% CI:0.50-1.09). Both double dose H2RAs and PPIs were effective at reducing the risk of endoscopic duodenal and gastric ulcers (RR=0.44; 95% CI:0.26-0.74 and RR=0.37;95% CI;0.27-0.51 respectively for gastric ulcer), and were better tolerated than misoprostol. REVIEWER'S CONCLUSIONS: Misoprostol, PPIs, and double dose H2RAs are effective at preventing chronic NSAID related endoscopic gastric and duodenal ulcers. Lower doses of misoprostol are less effective and are still associated with diarrhea. Only Misoprostol 800ug/day has been directly shown to reduce the risk of ulcer complications. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/10908548/Prevention_of_chronic_NSAID_induced_upper_gastrointestinal_toxicity_ L2 - https://doi.org/10.1002/14651858.CD002296 DB - PRIME DP - Unbound Medicine ER -