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Review Controversies in COX-2 selective inhibition. 2002
Simon LS, Smolen JS, Abramson SB, Appel G, Bombardier C, Brater DC, Breedveld FC, Brune K, Burmester GR, Crofford LJ, Dougados M, DuBois RN, Fitzgerald GA, Frishman W, García Rodríguez LA, Hochberg MC, Kalden JR, Laine L, Langman MJ, Prescott SM, van de Putte LB, Whelton A, White WB, Willaims GH. · Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. · J Rheumatol. · Pubmed #12136912 No free full text.
This publication has no abstract.
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Article Risk of cardiovascular events in patients receiving celecoxib: a meta-analysis of randomized clinical trials. 2007
White WB, West CR, Borer JS, Gorelick PB, Lavange L, Pan SX, Weiner E, Verburg KM. · Pat and Jim Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT, USA. · Am J Cardiol. · Pubmed #17196469 No free full text.
Abstract: Some nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 selective inhibitors, have been associated with increased cardiovascular (CV) events in recent clinical trials or observational studies. To determine whether the cyclooxygenase-2 selective inhibitor celecoxib affects CV risk, the incidence of CV events was analyzed in patients treated with celecoxib, placebo, or nonselective NSAIDs in the clinical trial database for celecoxib using defined Antiplatelet Trialists' Collaboration end points of nonfatal myocardial infarction, nonfatal stroke, and CV death. Patient data were derived from studies in osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, low back pain, and Alzheimer's disease. This meta-analysis included (1) 7,462 patients exposed to celecoxib 200 to 800 mg/day for 1,268 patient-years compared with 4,057 patients treated with placebo for 585 patient-years, and (2) 19,773 patients treated with celecoxib 200 to 800 mg/day for 5,651 patient-years compared with 13,990 patients treated with nonselective NSAIDs (diclofenac, ibuprofen, naproxen, ketoprofen, and loxoprofen) for 4,386 patient-years. CV events were adjudicated by a 3-member expert end point committee (WBW, JSB, PBG) blinded to treatment group and study. The incidence rates of the combined CV events were not significantly different between patients treated with celecoxib and placebo or between those treated with celecoxib and nonselective NSAIDs. Event rates were similar for adjudicated and nonadjudicated data. Dose of celecoxib, the use of aspirin, or the presence of CV risk factors did not alter these results. In conclusion, these analyses failed to demonstrate an increased CV risk with celecoxib relative to placebo and demonstrated a comparable rate of CV events with celecoxib treatment compared with nonselective NSAIDs.
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Article Effects of the cyclooxygenase-2 specific inhibitor valdecoxib versus nonsteroidal antiinflammatory agents and placebo on cardiovascular thrombotic events in patients with arthritis. 2004
White WB, Strand V, Roberts R, Whelton A. · Division of Hypertension and Clinical Pharmacology, Department of Medicine, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-3940, USA. · Am J Ther. · Pubmed #15266215 No free full text.
Abstract: There have been concerns that the risk of cardiovascular thrombotic events may be higher with cyclooxygenase (COX)-2-specific inhibitors than nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We evaluated cardiovascular event data for valdecoxib, a new COX-2-specific inhibitor in approximately 8000 patients with osteoarthritis and rheumatoid arthritis treated with this agent in randomized clinical trials. The incidence of cardiovascular thrombotic events (cardiac, cerebrovascular and peripheral vascular, or arterial thrombotic) was determined by analyzing pooled valdecoxib (10-80 mg daily), nonselective NSAID (diclofenac 75 mg bid, ibuprofen 800 mg tid, or naproxen 500 mg bid) and placebo data from 10 randomized osteoarthritis and rheumatoid arthritis trials that were 6-52 weeks in duration. The incidence rates of events were determined in all patients (n = 7934) and in users of low-dose (< or =325 mg daily) aspirin (n = 1051) and nonusers of aspirin (n = 6883). Crude and exposure-adjusted incidences of thrombotic events were similar for valdecoxib, NSAIDs, and placebo. The risk of serious thrombotic events was also similar for each valdecoxib dose. Thrombotic risk was consistently higher for users of aspirin users than nonusers of aspirin (placebo, 1.4% vs. 0%; valdecoxib, 1.7% vs. 0.2%; NSAIDs, 1.9% vs. 0.5%). The rates of events in users of aspirin were similar for all 3 treatment groups and across valdecoxib doses. Short- and intermediate-term treatment with therapeutic (10 or 20 mg daily) and supratherapeutic (40 or 80 mg daily) valdecoxib doses was not associated with an increased incidence of thrombotic events relative to nonselective NSAIDs or placebo in osteoarthritis and rheumatoid arthritis patients in controlled clinical trials.
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