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Gastroprotective therapy and risk of gastrointestinal ulcers: risk reduction by COX-2 therapy.
J Rheumatol. 2002 Mar; 29(3):467-73.JR

Abstract

OBJECTIVE

Proton pump inhibitors (PPI) and misoprostol decrease the risk of development of nonsteroidal antiinflammatory drug induced gastric ulcers and aid healing of upper gastrointestinal (GI) ulcers. H2 receptor antagonists (H2RA) are less effective for this task, but are widely used by patients and physicians for the treatment of GI symptoms and duodenal ulcers. Sucralfate is a weaker agent that is sometimes used for prophylaxis or treatment of upper GI ulcers. We investigated the effect of GI drugs and selective and nonselective NSAID on the incidence of GI ulcer development in a cohort of patients immediately after the release of celecoxib and rofecoxib to investigate the effect of confounding by indication when effective GI agents and cyclooxygenase 2 (COX-2)-specific inhibitors are prescribed to a high risk population.

METHODS

During a 6 month period of observation 8547 NSAID users were evaluated by mailed questionnaire concerning NSAID drug use and ulcer development. In the first half of 1999, patients took 12,177 separate NSAID courses. GI therapy that followed the development of upper GI ulcers was excluded from analysis. Ulcer reports were confirmed by followup validation.

RESULTS

GI drugs were used concomitantly in this population by 42% of patients using an NSAID. GI drugs were associated with an increased risk of ulcer. But this risk was confined to PPI (OR 4.1, 95% CI 2.95, 5.69), and not to other GI drugs. Overall, patients using nonselective NSAID compared to those taking COX-2-specific inhibitors had an increased risk of upper GI ulcers (OR 2.12, 95% CI 1.43, 3.34). Patients taking nonselective NSAID plus PPI were also at increased risk for upper GI ulcers compared to those taking nonselective NSAID alone (OR 5.09. 95% CI 3.88, 6.67). Similarly, the risk of upper GI ulcers was increased in the nonselective NSAID plus PPI group (OR 3.83, 95% CI 2.32, 6.31) compared to the COX-2 plus PPI group.

CONCLUSION

PPI use, but not other GI drug use, is a marker for increased susceptibility to ulcers among NSAID users. This risk of upper GI ulcers is increased in PPI users regardless of which NSAID is used (nonselective or COX-2-specific inhibitor). Although COX-2 use is associated with greater risk factors for upper GI ulcers due to channeling bias, COX-2 users have significantly fewer ulcers than equivalent nonselective NSAID users regardless of concomitant PPI utilization.

Authors+Show Affiliations

National Data Bank for Rheumatic Diseases-Arthritis Research Center Foundation and University of Kansas School of Medicine, Wichita 67214, USA. fwolfe@arthritis-research.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11908558

Citation

Wolfe, Frederick, et al. "Gastroprotective Therapy and Risk of Gastrointestinal Ulcers: Risk Reduction By COX-2 Therapy." The Journal of Rheumatology, vol. 29, no. 3, 2002, pp. 467-73.
Wolfe F, Anderson J, Burke TA, et al. Gastroprotective therapy and risk of gastrointestinal ulcers: risk reduction by COX-2 therapy. J Rheumatol. 2002;29(3):467-73.
Wolfe, F., Anderson, J., Burke, T. A., Arguelles, L. M., & Pettitt, D. (2002). Gastroprotective therapy and risk of gastrointestinal ulcers: risk reduction by COX-2 therapy. The Journal of Rheumatology, 29(3), 467-73.
Wolfe F, et al. Gastroprotective Therapy and Risk of Gastrointestinal Ulcers: Risk Reduction By COX-2 Therapy. J Rheumatol. 2002;29(3):467-73. PubMed PMID: 11908558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gastroprotective therapy and risk of gastrointestinal ulcers: risk reduction by COX-2 therapy. AU - Wolfe,Frederick, AU - Anderson,Janice, AU - Burke,Thomas A, AU - Arguelles,Lester M, AU - Pettitt,Dan, PY - 2002/3/23/pubmed PY - 2002/9/25/medline PY - 2002/3/23/entrez SP - 467 EP - 73 JF - The Journal of rheumatology JO - J Rheumatol VL - 29 IS - 3 N2 - OBJECTIVE: Proton pump inhibitors (PPI) and misoprostol decrease the risk of development of nonsteroidal antiinflammatory drug induced gastric ulcers and aid healing of upper gastrointestinal (GI) ulcers. H2 receptor antagonists (H2RA) are less effective for this task, but are widely used by patients and physicians for the treatment of GI symptoms and duodenal ulcers. Sucralfate is a weaker agent that is sometimes used for prophylaxis or treatment of upper GI ulcers. We investigated the effect of GI drugs and selective and nonselective NSAID on the incidence of GI ulcer development in a cohort of patients immediately after the release of celecoxib and rofecoxib to investigate the effect of confounding by indication when effective GI agents and cyclooxygenase 2 (COX-2)-specific inhibitors are prescribed to a high risk population. METHODS: During a 6 month period of observation 8547 NSAID users were evaluated by mailed questionnaire concerning NSAID drug use and ulcer development. In the first half of 1999, patients took 12,177 separate NSAID courses. GI therapy that followed the development of upper GI ulcers was excluded from analysis. Ulcer reports were confirmed by followup validation. RESULTS: GI drugs were used concomitantly in this population by 42% of patients using an NSAID. GI drugs were associated with an increased risk of ulcer. But this risk was confined to PPI (OR 4.1, 95% CI 2.95, 5.69), and not to other GI drugs. Overall, patients using nonselective NSAID compared to those taking COX-2-specific inhibitors had an increased risk of upper GI ulcers (OR 2.12, 95% CI 1.43, 3.34). Patients taking nonselective NSAID plus PPI were also at increased risk for upper GI ulcers compared to those taking nonselective NSAID alone (OR 5.09. 95% CI 3.88, 6.67). Similarly, the risk of upper GI ulcers was increased in the nonselective NSAID plus PPI group (OR 3.83, 95% CI 2.32, 6.31) compared to the COX-2 plus PPI group. CONCLUSION: PPI use, but not other GI drug use, is a marker for increased susceptibility to ulcers among NSAID users. This risk of upper GI ulcers is increased in PPI users regardless of which NSAID is used (nonselective or COX-2-specific inhibitor). Although COX-2 use is associated with greater risk factors for upper GI ulcers due to channeling bias, COX-2 users have significantly fewer ulcers than equivalent nonselective NSAID users regardless of concomitant PPI utilization. SN - 0315-162X UR - https://www.unboundmedicine.com/medline/citation/11908558/Gastroprotective_therapy_and_risk_of_gastrointestinal_ulcers:_risk_reduction_by_COX_2_therapy_ DB - PRIME DP - Unbound Medicine ER -