Lower Gastrointestinal Events in a Double-Blind Trial of the Cyclo-Oxygenase-2 Selective Inhibitor Etoricoxib and the Traditional Nonsteroidal Anti-Inflammatory Drug Diclofenac

Loren Laine, Sean P. Curtis, Michael Langman, Dennis M. Jensen, Byron Cryer, Amarjot Kaur, Christopher P. Cannon

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Background & Aims: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause lower gastrointestinal (GI) clinical events such as bleeding. Cyclo-oxygenase (COX)-2 selective inhibitors decrease upper GI events, but no prospective trial has prespecified assessment of lower GI clinical events. Methods: Patients ≥50 years old with osteoarthritis or rheumatoid arthritis were randomly assigned to etoricoxib (60 or 90 mg qd) or diclofenac (150 mg qd). Lower GI clinical events, confirmed by a blinded adjudication committee, included perforation or obstruction requiring hospitalization or bleeding (gross or occult rectal bleeding without upper GI cause associated with hypotension, orthostatic changes in heart rate [>20 beats per minute] or blood pressure [>20 mmHg systolic or >10 mmHg diastolic], hemoglobin drop ≥2 g/dl, or transfusion; or observed active bleeding or stigmata of hemorrhage). Results: We enrolled 34,701 patients with mean duration of therapy of 18 months. Rates were 0.32 and 0.38 lower GI clinical events per 100 patient-years for etoricoxib and diclofenac (hazard ratio [HR] = 0.84; 95% confidence interval [CI], 0.63-1.13). Bleeding was the most common event (rates of 0.19 and 0.23 per 100 patient-years, respectively). Multivariable analysis revealed significant risk factors to be prior lower GI event (HR = 4.06; 95% CI, 2.93-5.62) and age ≥65 years (HR = 1.98; 95% CI, 1.45-2.71). Conclusions: A statistically significant decrease in lower GI clinical events was not seen with the COX-2 selective inhibitor etoricoxib versus the traditional NSAID diclofenac. The risk of a lower GI clinical event with NSAID use seems to be constant over time, and the major risk factors are a prior lower GI event and older age.

Original languageEnglish (US)
Pages (from-to)1517-1525
Number of pages9
JournalGastroenterology
Volume135
Issue number5
DOIs
StatePublished - Nov 2008

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etoricoxib
Diclofenac
Prostaglandin-Endoperoxide Synthases
Anti-Inflammatory Agents
Hemorrhage
Pharmaceutical Preparations
Confidence Intervals
Christianity
Orthostatic Hypotension
Osteoarthritis
Rheumatoid Arthritis
Hemoglobins
Hospitalization
Heart Rate

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Lower Gastrointestinal Events in a Double-Blind Trial of the Cyclo-Oxygenase-2 Selective Inhibitor Etoricoxib and the Traditional Nonsteroidal Anti-Inflammatory Drug Diclofenac. / Laine, Loren; Curtis, Sean P.; Langman, Michael; Jensen, Dennis M.; Cryer, Byron; Kaur, Amarjot; Cannon, Christopher P.

In: Gastroenterology, Vol. 135, No. 5, 11.2008, p. 1517-1525.

Research output: Contribution to journalArticle

Laine, Loren ; Curtis, Sean P. ; Langman, Michael ; Jensen, Dennis M. ; Cryer, Byron ; Kaur, Amarjot ; Cannon, Christopher P. / Lower Gastrointestinal Events in a Double-Blind Trial of the Cyclo-Oxygenase-2 Selective Inhibitor Etoricoxib and the Traditional Nonsteroidal Anti-Inflammatory Drug Diclofenac. In: Gastroenterology. 2008 ; Vol. 135, No. 5. pp. 1517-1525.
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abstract = "Background & Aims: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause lower gastrointestinal (GI) clinical events such as bleeding. Cyclo-oxygenase (COX)-2 selective inhibitors decrease upper GI events, but no prospective trial has prespecified assessment of lower GI clinical events. Methods: Patients ≥50 years old with osteoarthritis or rheumatoid arthritis were randomly assigned to etoricoxib (60 or 90 mg qd) or diclofenac (150 mg qd). Lower GI clinical events, confirmed by a blinded adjudication committee, included perforation or obstruction requiring hospitalization or bleeding (gross or occult rectal bleeding without upper GI cause associated with hypotension, orthostatic changes in heart rate [>20 beats per minute] or blood pressure [>20 mmHg systolic or >10 mmHg diastolic], hemoglobin drop ≥2 g/dl, or transfusion; or observed active bleeding or stigmata of hemorrhage). Results: We enrolled 34,701 patients with mean duration of therapy of 18 months. Rates were 0.32 and 0.38 lower GI clinical events per 100 patient-years for etoricoxib and diclofenac (hazard ratio [HR] = 0.84; 95{\%} confidence interval [CI], 0.63-1.13). Bleeding was the most common event (rates of 0.19 and 0.23 per 100 patient-years, respectively). Multivariable analysis revealed significant risk factors to be prior lower GI event (HR = 4.06; 95{\%} CI, 2.93-5.62) and age ≥65 years (HR = 1.98; 95{\%} CI, 1.45-2.71). Conclusions: A statistically significant decrease in lower GI clinical events was not seen with the COX-2 selective inhibitor etoricoxib versus the traditional NSAID diclofenac. The risk of a lower GI clinical event with NSAID use seems to be constant over time, and the major risk factors are a prior lower GI event and older age.",
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AU - Laine, Loren

AU - Curtis, Sean P.

AU - Langman, Michael

AU - Jensen, Dennis M.

AU - Cryer, Byron

AU - Kaur, Amarjot

AU - Cannon, Christopher P.

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AB - Background & Aims: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause lower gastrointestinal (GI) clinical events such as bleeding. Cyclo-oxygenase (COX)-2 selective inhibitors decrease upper GI events, but no prospective trial has prespecified assessment of lower GI clinical events. Methods: Patients ≥50 years old with osteoarthritis or rheumatoid arthritis were randomly assigned to etoricoxib (60 or 90 mg qd) or diclofenac (150 mg qd). Lower GI clinical events, confirmed by a blinded adjudication committee, included perforation or obstruction requiring hospitalization or bleeding (gross or occult rectal bleeding without upper GI cause associated with hypotension, orthostatic changes in heart rate [>20 beats per minute] or blood pressure [>20 mmHg systolic or >10 mmHg diastolic], hemoglobin drop ≥2 g/dl, or transfusion; or observed active bleeding or stigmata of hemorrhage). Results: We enrolled 34,701 patients with mean duration of therapy of 18 months. Rates were 0.32 and 0.38 lower GI clinical events per 100 patient-years for etoricoxib and diclofenac (hazard ratio [HR] = 0.84; 95% confidence interval [CI], 0.63-1.13). Bleeding was the most common event (rates of 0.19 and 0.23 per 100 patient-years, respectively). Multivariable analysis revealed significant risk factors to be prior lower GI event (HR = 4.06; 95% CI, 2.93-5.62) and age ≥65 years (HR = 1.98; 95% CI, 1.45-2.71). Conclusions: A statistically significant decrease in lower GI clinical events was not seen with the COX-2 selective inhibitor etoricoxib versus the traditional NSAID diclofenac. The risk of a lower GI clinical event with NSAID use seems to be constant over time, and the major risk factors are a prior lower GI event and older age.

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