• 1
    Hawker GA, Katz JN, Solomon DH. The patient's perspective on the recall of Vioxx. J Rheumatol 2006; 33: 10828.
  • 2
    US Food and Drug Administration. Alert for healthcare professionals: non-selective non-steroidal anti-inflammatory drugs (NSAIDs). 2005. URL:
  • 3
    Antman EM, Bennett JS, Daugherty A, Furberg C, Roberts H, Taubert KA, for the American Heart Association. Use of nonsteroidal antiinflammatory drugs: an update for clinicians. A scientific statement from the American Heart Association. Circulation 2007; 115: 163442.
  • 4
    Bombardieri S, Cattani P, Ciabattoni G, Di Munno O, Pasero G, Patrono C, et al. The synovial prostaglandin system in chronic inflammatory arthritis: differential effects of steroidal and nonsteroidal anti-inflammatory drugs. Br J Pharmacol 1981; 73: 893901.
  • 5
    Peplow PV. Properties and actions of non-steroidal anti-inflammatory drugs, including their effects on prostaglandin and macromolecular biosynthesis. Prostaglandins Leukot Essent Fatty Acids 1988; 33: 23952.
  • 6
    Simmons DL, Botting RM, Hla T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev 2004; 56: 387437.
  • 7
    Day RO, McLachlan AJ, Graham GG, Williams KM. Pharmacokinetics of nonsteroidal anti-inflammatory drugs in synovial fluid. Clin Pharmacokinet 1999; 36: 191210.
  • 8
    FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 2001; 345: 43342.
  • 9
    Williams HJ, Ward JR, Egger MJ, Neuner R, Brooks RH, Clegg DO, et al. Comparison of naproxen and acetaminophen in a two-year study of treatment of osteoarthritis of the knee. Arthritis Rheum 1993; 36: 1196206.
  • 10
    Wolfe F, Zhao S, Lane N. Preference for nonsteroidal antiinflammatory drugs over acetaminophen by rheumatic disease patients: a survey of 1,799 patients with osteoarthritis, rheumatoid arthritis, and fibromyalgia. Arthritis Rheum 2000; 43: 37885.
  • 11
    Bradley JD, Brandt KD, Katz BP, Kalasinski LA, Ryan SI. Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee. N Engl J Med 1991; 325: 8791.
  • 12
    Pincus T, Koch GG, Sokka T, Lefkowith J, Wolfe F, Jordan JM, et al. A randomized, double-blind, crossover clinical trial of diclofenac plus misoprostol versus acetaminophen in patients with osteoarthritis of the hip or knee. Arthritis Rheum 2001; 44: 158798.
  • 13
    Case JP, Baliunas AJ, Block JA. Lack of efficacy of acetaminophen in treating symptomatic knee osteoarthritis: a randomized, double-blind, placebo-controlled comparison trial with diclofenac sodium. Arch Intern Med 2003; 163: 16978.
  • 14
    Boureau F, Schneid H, Zeghari N, Wall R, Bourgeois P. The IPSO study: ibuprofen, paracetamol study in osteoarthritis. A randomised comparative clinical study comparing the efficacy and safety of ibuprofen and paracetamol analgesic treatment of osteoarthritis of the knee or hip. Ann Rheum Dis 2004; 63: 102834.
  • 15
    Pincus T, Koch G, Lei H, Mangal B, Sokka T, Moskowitz R, et al. Patient Preference for Placebo, Acetaminophen (paracetamol) or Celecoxib Efficacy Studies (PACES): two randomised, double blind, placebo controlled, crossover clinical trials in patients with knee or hip osteoarthritis. Ann Rheum Dis 2004; 63: 9319.
  • 16
    March L, Irwig L, Schwarz J, Simpson J, Chock C, Brooks P. n of 1 trials comparing a non-steroidal anti-inflammatory drug with paracetamol in osteoarthritis. BMJ 1994; 309: 10415.
  • 17
    Schnitzer TJ, Kamin M, Olson WH. Tramadol allows reduction of naproxen dose among patients with naproxen-responsive osteoarthritis pain: a randomized, double-blind, placebo-controlled study. Arthritis Rheum 1999; 42: 13707.
  • 18
    Caldwell JR, Hale ME, Boyd RE, Hague JM, Iwan T, Shi M, et al. Treatment of osteoarthritis pain with controlled release oxycodone or fixed combination oxycodone plus acetaminophen added to nonsteroidal antiinflammatory drugs: a double blind, randomized, multicenter, placebo controlled trial. J Rheumatol 1999; 26: 8629.
  • 19
    Brandt KD, Bradley JD. Should the initial drug be used to treat osteoarthritis pain be a nonsteroidal antiinflammatory drug? J Rheumatol 2001; 28: 46773.
  • 20
    Felson DT. The verdict favors nonsteroidal antiinflammatory drugs for treatment of osteoarthritis and a plea for more evidence on other treatments [editorial]. Arthritis Rheum 2001; 44: 147780.
  • 21
    Moskowitz RW. Osteoarthritis: simple analgesics versus nonsteroidal antiinflammatory drugs. J Rheumatol 2001; 28: 9324.
  • 22
    Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells G. Acetaminophen for osteoarthritis. Cochrane Database Syst Rev 2006; 1: CD004257.
  • 23
    American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum 2000; 43: 190515.
  • 24
    Zhang W, Doherty M, Arden N, Bannwarth B, Bijlsma J, Gunther KP, et al. EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2005; 64: 66981.
  • 25
    Huskisson EC, Woolf DL, Balme HW, Scott J, Franklin S. Four new anti-inflammatory drugs: responses and variations. Br Med J 1976; 1: 10489.
  • 26
    Simpson J, Golding DN, Freeman AM, Cooke D, Hooper PA, Jamieson V, et al. A large multicentre, parallel group, double-blind study comparing tenoxicam and piroxicam in the treatment of osteoarthritis and rheumatoid arthritis. Br J Clin Pract 1989; 43: 32833.
  • 27
    Chou R, Helfand M, Peterson K, Dana T, Roberts C. Comparative effectiveness and safety of analgesics for osteoarthritis: comparative effectiveness review no. 4 (prepared by the Oregon Evidence-based Practice Center under contract no. 290-02-0024). Rockville (MD): Agency for Healthcare Research and Quality; 2006. URL:
  • 28
    Geba GP, Weaver AL, Polis AB, Dixon ME, Schnitzer TJ, for the VACT Group. Efficacy of rofecoxib, celecoxib, and acetaminophen in osteoarthritis of the knee: a randomized trial [published erratum appears in JAMA 2002;287:989]. JAMA 2002; 287: 6471.
  • 29
    Bensen W, Weaver A, Espinoza L, Zhao WW, Riley W, Paperiello B, et al. Efficacy and safety of valdecoxib in treating the signs and symptoms of rheumatoid arthritis: a randomized, controlled comparison with placebo and naproxen. Rheumatology (Oxford) 2002; 41: 100816.
  • 30
    Goldstein JL, Correa P, Zhao WW, Burr AM, Hubbard RC, Verburg KM, et al. Reduced incidence of gastroduodenal ulcers with celecoxib, a novel cyclooxygenase-2 inhibitor, compared to naproxen in patients with arthritis. Am J Gastroenterol 2001; 96: 101927.
    Direct Link:
  • 31
    Kivitz AJ, Moskowitz RW, Woods E, Hubbard RC, Verburg KM, Lefkowith JB, et al. Comparative efficacy and safety of celecoxib and naproxen in the treatment of osteoarthritis of the hip. J Int Med Res 2001; 29: 46779.
  • 32
    Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis. The CLASS study: a randomized controlled trial. JAMA 2000; 284: 124755.
  • 33
    Deeks JJ, Smith LA, Bradley MD. Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomised controlled trials. BMJ 2002; 325: 619.
  • 34
    Moore RA, Derry S, Makinson GT, McQuay HJ. Tolerability and adverse events in clinical trials of celecoxib in osteoarthritis and rheumatoid arthritis: systematic review and meta-analysis of information from company clinical trial reports [published erratum appears in Arthritis Res Ther 2006;8:401]. Arthritis Res Ther 2005; 7: R64465.
  • 35
    Singh G, Fort JG, Goldstein JL, Levy RA, Hanrahan PS, Bello AE, et al, and the SUCCESS-I Investigators. Celecoxib versus naproxen and diclofenac in osteoarthritis patients: SUCCESS-I study [published erratum appears in Am J Med 2006;119:801]. Am J Med 2006; 119: 25566.
  • 36
    Laine L, Harper S, Simon T, Bath R, Johanson J, Schwartz H, et al, for the Rofecoxib Osteoarthritis Endoscopy Study Group. A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis. Gastroenterology 1999; 117: 77683.
  • 37
    Saag K, van der Heijde D, Fisher C, Samara A, DeTora L, Bolognese J, et al, for the Osteoarthritis Studies Group. Rofecoxib, a new cyclooxygenase 2 inhibitor, shows sustained efficacy, comparable with other nonsteroidal anti-inflammatory drugs: a 6-week and a 1-year trial in patients with osteoarthritis. Arch Fam Med 2000; 9: 112434.
  • 38
    Day R, Morrison B, Luza A, Castaneda O, Strusberg A, Nahir M, et al, for the Rofecoxib/Ibuprofen Comparator Study Group. A randomized trial of the efficacy and tolerability of the COX-2 inhibitor rofecoxib vs ibuprofen in patients with osteoarthritis. Arch Intern Med 2000; 160: 17817.
  • 39
    Cannon GW, Caldwell JR, Holt P, McLean B, Seidenberg B, Bolognese J, et al, for the Rofecoxib Phase III Protocol 035 Study Group. Rofecoxib, a specific inhibitor of cyclooxygenase 2, with clinical efficacy comparable with that of diclofenac sodium: results of a one-year, randomized, clinical trial in patients with osteoarthritis of the knee and hip. Arthritis Rheum 2000; 43: 97887.
  • 40
    Truitt KE, Sperling RS, Ettinger WH Jr, Greenwald M, DeTora L, Zeng Q, et al, for the Phase III Rofecoxib Geriatric Study Group. A multicenter, randomized, controlled trial to evaluate the safety profile, tolerability, and efficacy of rofecoxib in advanced elderly patients with osteoarthritis. Aging (Milano) 2001; 13: 11221.
  • 41
    Niccoli L, Bellino S, Cantini F. Renal tolerability of three commonly employed non-steroidal anti-inflammatory drugs in elderly patients with osteoarthritis. Clin Exp Rheumatol 2002; 20: 2017.
  • 42
    Myllykangas-Luosujarvi R, Lu HS, Chen SL, Choon D, Amante C, Chow CT, et al, for the Naproxen 901 OF Study Group and the Naproxen 901 OC Study Group. Comparison of low-dose rofecoxib versus 1000 mg naproxen in patients with osteoarthritis: results of two randomized treatment trials of six weeks duration. Scand J Rheumatol 2002; 31: 33744.
  • 43
    Lisse JR, Perlman M, Johansson G, Shoemaker JR, Schechtman J, Skalky CS, et al, for the ADVANTAGE Study Group. Gastrointestinal tolerability and effectiveness of rofecoxib versus naproxen in the treatment of osteoarthritis: a randomized, controlled trial. Ann Intern Med 2003; 139: 53946.
  • 44
    Kivitz AJ, Greenwald MW, Cohen SB, Polis AB, Najarian DK, Dixon ME, et al, for the Protocol 085 Study Investigators. Efficacy and safety of rofecoxib 12.5 mg versus nabumetone 1,000 mg in patients with osteoarthritis of the knee: a randomized controlled trial. J Am Geriatr Soc 2004; 52: 66674.
  • 45
    Geusens PP, Truitt K, Sfikakis P, Zhao PL, DeTora L, Shingo S, et al. A placebo and active comparator-controlled trial of rofecoxib for the treatment of rheumatoid arthritis. Scand J Rheumatol 2002; 31: 2308.
  • 46
    Garner SE, Fidan DD, Frankish RR, Judd MG, Towheed TE, Wells G, et al. Rofecoxib for rheumatoid arthritis. Cochrane Database Syst Rev 2005; 1: CD003685.
  • 47
    Makarowski W, Zhao WW, Bevirt T, Recker DP. Efficacy and safety of the COX-2 specific inhibitor valdecoxib in the management of osteoarthritis of the hip: a randomized, double-blind, placebo-controlled comparison with naproxen. Osteoarthritis Cartilage 2002; 10: 2906.
  • 48
    Kivitz A, Eisen G, Zhao WW, Bevirt T, Recker DP. Randomized placebo-controlled trial comparing efficacy and safety of valdecoxib with naproxen in patients with osteoarthritis. J Fam Pract 2002; 51: 5307.
  • 49
    Sikes DH, Agrawal NM, Zhao WW, Kent JD, Recker DP, Verburg KM. Incidence of gastroduodenal ulcers associated with valdecoxib compared with that of ibuprofen and diclofenac in patients with osteoarthritis. Eur J Gastroenterol Hepatol 2002; 14: 110111.
  • 50
    Pavelka K, Recker DP, Verburg KM. Valdecoxib is as effective as diclofenac in the management of rheumatoid arthritis with a lower incidence of gastroduodenal ulcers: results of a 26-week trial. Rheumatology (Oxford) 2003; 42: 120715.
  • 51
    Whelton A, Fort JG, Puma JA, Normandin D, Bello AE, Verburg KM, for the SUCCESS VI Study Group. Cyclooxygenase-2–specific inhibitors and cardiorenal function: a randomized, controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients [published erratum appears in Am J Ther 2001;8:220]. Am J Ther 2001; 8: 8595.
  • 52
    Whelton A, White WB, Bello AE, Puma JA, Fort JG, and the SUCCESS-VII Investigators. Effects of celecoxib and rofecoxib on blood pressure and edema in patients > or =65 years of age with systemic hypertension and osteoarthritis. Am J Cardiol 2002; 90: 95963.
  • 53
    McKenna F, Borenstein D, Wendt H, Wallemark C, Lefkowith JB, Geis GS. Celecoxib versus diclofenac in the management of osteoarthritis of the knee. Scand J Rheumatol 2001; 30: 118.
  • 54
    Bianchi M, Broggini M. A randomised, double-blind, clinical trial comparing the efficacy of nimesulide, celecoxib and rofecoxib in osteoarthritis of the knee. Drugs 2003; 63 Suppl 1: 3746.
  • 55
    Gibofsky A, Williams GW, McKenna F, Fort JG. Comparing the efficacy of cyclooxygenase 2–specific inhibitors in treating osteoarthritis: appropriate trial design considerations and results of a randomized, placebo-controlled trial. Arthritis Rheum 2003; 48: 310211.
  • 56
    Campbell CL, Smyth S, Montalescot G, Steinhubl SR. Aspirin dose for the prevention of cardiovascular disease: a systematic review. JAMA 2007; 297: 201824.
  • 57
    US Food and Drug Administration. Concomitant use of ibuprofen and aspirin: potential for attenuation of the anti-platelet effect of aspirin. 2006. URL:
  • 58
    Capone ML, Sciulli MG, Tacconelli S, Grana M, Ricciotti E, Renda G, et al. Pharmacodynamic interaction of naproxen with low-dose aspirin in healthy subjects. J Am Coll Cardiol 2005; 45: 1295301.
  • 59
    Grosser T, Fries S, FitzGerald GA. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin Invest 2006; 116: 415.
  • 60
    Cipollone F, Fazia M, Mezzetti A. Novel determinants of plaque instability. J Thromb Haemost 2005; 3: 196275.
  • 61
    Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ 2006; 332: 13028.
  • 62
    McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA 2006; 296: 163344.
  • 63
    Hernandez-Diaz S, Varas-Lorenzo C, Garcia Rodriguez LA. Non-steroidal antiinflammatory drugs and the risk of acute myocardial infarction. Basic Clin Pharmacol Toxicol 2006; 98: 26674.
  • 64
    Antman EM, DeMets D, Loscalzo J. Cyclooxygenase inhibition and cardiovascular risk. Circulation 2005; 112: 75970.
  • 65
    FitzGerald GA. COX-2 in play at the AHA and the FDA. Trends Pharmacol Sci 2007; 28: 3037.
  • 66
    Scott PA, Kingsley GH, Smith CM, Choy EH, Scott DL. Non-steroidal anti-inflammatory drugs and myocardial infarctions: comparative systematic review of evidence from observational studies and randomised controlled trials. Ann Rheum Dis 2007; 66: 1296304.
  • 67
    Hippisley-Cox J, Coupland C. Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ 2005; 330: 1366.
  • 68
    Graham DJ, Campen D, Hui R, Spence M, Cheetham C, Levy G, et al. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet 2005; 365: 47581.
  • 69
    Solomon DH, Schneeweiss S, Glynn RJ, Kiyota Y, Levin R, Mogun H, et al. Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation 2004; 109: 206873.
  • 70
    Aw TJ, Haas SJ, Liew D, Krum H. Meta-analysis of cyclooxygenase-2 inhibitors and their effects on blood pressure. Arch Intern Med 2005; 165: 4906.
  • 71
    Glaser K, Sung ML, O'Neill K, Belfast M, Hartman D, Carlson R, et al. Etodolac selectively inhibits human prostaglandin G/H synthase 2 (PGHS-2) versus human PGHS-1. Eur J Pharmacol 1995; 281: 10711.
  • 72
    Solomon SD, Pfeffer MA, McMurray JJ, Fowler R, Finn P, Levin B, et al, and the APC and PreSAP Trial Investigators. Effect of celecoxib on cardiovascular events and blood pressure in two trials for the prevention of colorectal adenomas. Circulation 2006; 114: 102835.
  • 73
    Griffoni C, Spisni E, Strillacci A, Toni M, Bachschmid MM, Tomasi V. Selective inhibition of prostacyclin synthase activity by rofecoxib. J Cell Mol Med 2007; 11: 32738.
  • 74
    Gottesdiener K, Schnitzer T, Fisher C, Bockow B, Markenson J, Ko A, et al, for the Protocol 007 Study Group. Results of a randomized, dose-ranging trial of etoricoxib in patients with osteoarthritis [published erratum appears in Rheumatology (Oxford) 2003;42:814]. Rheumatology (Oxford) 2002; 41: 105261.
  • 75
    Nussmeier NA, Whelton AA, Brown MT, Langford RM, Hoeft A, Parlow JL, et al. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med 2005; 352: 108191.
  • 76
    Farkouh ME, Greenberg JD, Jeger RV, Ramanathan K, Verheugt FW, Chesebro JH, et al. Cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib. Ann Rheum Dis 2007; 66: 76470.
  • 77
    Moore RA, Derry S, McQuay HJ. Cyclo-oxygenase-2 selective inhibitors and nonsteroidal anti-inflammatory drugs: balancing gastrointestinal and cardiovascular risk. BMC Musculoskelet Disord 2007; 8: 73.
  • 78
    Huerta C, Varas-Lorenzo C, Castellsague J, Garcia Rodriguez LA. Non-steroidal anti-inflammatory drugs and risk of first hospital admission for heart failure in the general population. Heart 2006; 92: 16105.
  • 79
    Hudson M, Richard H, Pilote L. Differences in outcomes of patients with congestive heart failure prescribed celecoxib, rofecoxib, or non-steroidal anti-inflammatory drugs: population based study. BMJ 2005; 330: 1370.
  • 80
    Zhang J, Ding EL, Song Y. Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomized trials. JAMA 2006; 296: 161932.
  • 81
    Singh G, Triadafilopoulos G. Epidemiology of NSAID induced gastrointestinal complications. J Rheumatol Suppl 1999; 56: 1824.
  • 82
    Bollini P, Garcia Rodriguez LA, Perez Gutthann S, Walker AM. The impact of research quality and study design on epidemiologic estimates of the effect of nonsteroidal anti-inflammatory drugs on upper gastrointestinal tract disease. Arch Intern Med 1992; 152: 128995.
  • 83
    Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs: a meta-analysis. Ann Intern Med 1991; 115: 78796.
  • 84
    Hernandez-Diaz S, Rodriguez LA. Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal tract bleeding/perforation: an overview of epidemiologic studies published in the 1990s. Arch Intern Med 2000; 160: 20939.
  • 85
    Ofman JJ, MacLean CH, Straus WL, Morton SC, Berger ML, Roth EA, et al. A metaanalysis of severe upper gastrointestinal complications of nonsteroidal antiinflammatory drugs. J Rheumatol 2002; 29: 80412.
  • 86
    Gutthann SP, Garcia Rodriguez LA, Raiford DS. Individual nonsteroidal antiinflammatory drugs and other risk factors for upper gastrointestinal bleeding and perforation. Epidemiology 1997; 8: 1824.
  • 87
    Singh G, Ramey DR, Morfeld D, Shi H, Hatoum HT, Fries JF. Gastrointestinal tract complications of nonsteroidal anti-inflammatory drug treatment in rheumatoid arthritis: a prospective observational cohort study. Arch Intern Med 1996; 156: 15306.
  • 88
    Fries JF, Williams CA, Bloch DA, Michel BA. Nonsteroidal anti-inflammatory drug-associated gastropathy: incidence and risk factor models. Am J Med 1991; 91: 21322.
  • 89
    Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al, for The VIGOR Study Group. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med 2000; 343: 15208.
  • 90
    Silverstein FE, Graham DY, Senior JR, Davies HW, Struthers BJ, Bottman RM, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1995; 123: 2419.
  • 91
    Garcia Rodriguez LA, Barreales Tolosa L. Risk of upper gastrointestinal complications among users of traditional NSAIDs and COXIBs in the general population. Gastroenterology 2007; 132: 498506.
  • 92
    Schoenfeld P. Gastrointestinal safety profile of meloxicam: a meta-analysis and systematic review of randomized controlled trials. Am J Med 1999; 107: 48S54S.
  • 93
    Fleischmann RM. Clinical efficacy and safety of nabumetone in rheumatoid arthritis and osteoarthritis. J Rheumatol Suppl 1992; 36: 3240.
  • 94
    Weideman RA, Kelly KC, Kazi S, Cung A, Roberts KW, Smith HJ, et al. Risks of clinically significant upper gastrointestinal events with etodolac and naproxen: a historical cohort analysis. Gastroenterology 2004; 127: 13228.
  • 95
    Mann JL, Evans TS. Gastrointestinal-related complications in a long-term care population taking NSAIDs versus COX-2 inhibitor therapy. Consult Pharm 2004; 19: 60213.
  • 96
    Richy F, Bruyere O, Ethgen O, Rabenda V, Bouvenot G, Audran M, et al. Time dependent risk of gastrointestinal complications induced by non-steroidal anti-inflammatory drug use: a consensus statement using a meta-analytic approach. Ann Rheum Dis 2004; 63: 75966.
  • 97
    Lanza F, Rack MF, Doucette M, Ekholm B, Goldlust B, Wilson R. An endoscopic comparison of the gastroduodenal injury seen with salsalate and naproxen. J Rheumatol 1989; 16: 15704.
  • 98
    Laine L, Curtis SP, Cryer B, Kaur A, Cannon CP, for the MEDAL Steering Committee. Assessment of upper gastrointestinal safety of etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet 2007; 369: 46573.
  • 99
    Schnitzer TJ, Burmester GR, Mysler E, Hochberg MC, Doherty M, Ehrsam E, et al, for the TARGET Study Group. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial. Lancet 2004; 364: 66574.
  • 100
    National Institute for Clinical Excellence (NICE). NICE guidelines: number 27. Guidance on the use of cyclooxygenase (Cox) II selective inhibitors, celecoxib, rofecoxib, meloxicam and etodolac for osteoarthritis and rheumatoid arthritis. 2007. URL:
  • 101
    Goldkind L, Witter J, editors. Statistical reviewer briefing document for the advisory committee. 2000. URL:
  • 102
    Hrachovec JB, Mora M. Reporting of 6-month vs 12-month data in a clinical trial of celecoxib [letter]. JAMA 2001; 286: 2398.
  • 103
    Juni P, Rutjes AW, Dieppe PA. Are selective COX 2 inhibitors superior to traditional non steroidal anti-inflammatory drugs? [published erratum appears in BMJ 2002;324:1538] [letter]. BMJ 2002; 324: 12878.
  • 104
    Langman MJ, Jensen DM, Watson DJ, Harper SE, Zhao PL, Quan H, et al. Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs. JAMA 1999; 282: 192933.
  • 105
    Goldstein JL, Silverstein FE, Agrawal NM, Hubbard RC, Kaiser J, Maurath CJ, et al. Reduced risk of upper gastrointestinal ulcer complications with celecoxib, a novel COX-2 inhibitor. Am J Gastroenterol 2000; 95: 168190.
    Direct Link:
  • 106
    Koch M, Dezi A, Ferrario F, Capurso I. Prevention of nonsteroidal anti-inflammatory drug-induced gastrointestinal mucosal injury: a meta-analysis of randomized controlled clinical trials. Arch Intern Med 1996; 156: 232132.
  • 107
    Taha AS, Hudson N, Hawkey CJ, Swannell AJ, Trye PN, Cottrell J, et al. Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal antiinflammatory drugs. N Engl J Med 1996; 334: 14359.
  • 108
    Yeomans ND, Tulassay Z, Juhasz L, Racz I, Howard JM, van Rensburg CJ, et al, for The Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) Study Group. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. N Engl J Med 1998; 338: 71926.
  • 109
    Hawkey CJ, Karrasch JA, Szczepanski L, Walker DG, Barkum A, Swannell AJ, et al, for the Omeprazole versus Misoprostol for NSAID-Induced Ulcer Management (OMNIUM) Study Group. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. N Engl J Med 1998; 338: 72734.
  • 110
    Chen JT, Pucino F, Resman-Targoff BH. Celecoxib versus a non-selective NSAID plus proton-pump inhibitor: what are the considerations? J Pain Palliat Care Pharmacother 2006; 20: 1132.
  • 111
    Hooper L, Brown TJ, Elliott R, Payne K, Roberts C, Symmons D. The effectiveness of five strategies for the prevention of gastrointestinal toxicity induced by non-steroidal anti-inflammatory drugs: systematic review. BMJ 2004; 329: 948.
  • 112
    Chan FK, Wong VW, Suen BY, Wu JC, Ching JY, Hung LC, et al. Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial. Lancet 2007; 369: 16216.
  • 113
    Ray WA, Chung CP, Stein CM, Smalley WE, Hall K, Arbogast PG, et al. Risk of peptic ulcer hospitalizations in users of NSAIDs with gastroprotective cotherapy versus coxibs. Gastroenterology 2007; 133: 7908.
  • 114
    Cannon CP, Curtis SP, FitzGerald GA, Krum H, Kaur A, Bolognese JA, et al, for the MEDAL Steering Committee. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet 2006; 368: 177181.
  • 115
    Scheiman JM, Fendrick AM. Summing the risk of NSAID therapy. Lancet 2007; 369: 15801.
  • 116
    Clive DM, Stoff JS. Renal syndromes associated with nonsteroidal antiinflammatory drugs. N Engl J Med 1984; 310: 56372.
  • 117
    Swan SK, Rudy DW, Lasseter KC, Ryan CF, Buechel KL, Lambrecht LJ, et al. Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet: a randomized, controlled trial. Ann Intern Med 2000; 133: 19.
  • 118
    Rossat J, Maillard M, Nussberger J, Brunner HR, Burnier M. Renal effects of selective cyclooxygenase-2 inhibition in normotensive salt-depleted subjects. Clin Pharmacol Ther 1999; 66: 7684.
  • 119
    Catella-Lawson F, McAdam B, Morrison BW, Kapoor S, Kujubu D, Antes L, et al. Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids. J Pharmacol Exp Ther 1999; 289: 73541.
  • 120
    Griffin MR, Yared A, Ray WA. Nonsteroidal antiinflammatory drugs and acute renal failure in elderly persons. Am J Epidemiol 2000; 151: 48896.
  • 121
    Perez Gutthann S, Garcia Rodriguez LA, Raiford DS, Duque Oliart A, Ris Romeu J. Nonsteroidal anti-inflammatory drugs and the risk of hospitalization for acute renal failure. Arch Intern Med 1996; 156: 24339.
  • 122
    Perneger TV, Whelton PK, Klag MJ. Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs. N Engl J Med 1994; 331: 16759.
  • 123
    Sandler DP, Burr FR, Weinberg CR. Nonsteroidal anti-inflammatory drugs and the risk for chronic renal disease. Ann Intern Med 1991; 115: 16572.
  • 124
    Johnson AG, Nguyen TV, Day RO. Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis. Ann Intern Med 1994; 121: 289300.
  • 125
    Bjorkman D. Nonsteroidal anti-inflammatory drug-associated toxicity of the liver, lower gastrointestinal tract, and esophagus. Am J Med 1998; 105: 17S21S.
  • 126
    Teoh NC, Farrell GC. Hepatotoxicity associated with non-steroidal anti-inflammatory drugs. Clin Liver Dis 2003; 7: 40113.
  • 127
    Rubenstein JH, Laine L. Systematic review: the hepatotoxicity of non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 2004; 20: 37380.
  • 128
    Goldkind L, Laine L. A systematic review of NSAIDs withdrawn from the market due to hepatotoxicity: lessons learned from the bromfenac experience. Pharmacoepidemiol Drug Saf 2006; 15: 21320.
  • 129
    Therapeutic Goods Administration. Urgent advice regarding management of patients taking lumiracoxib (Prexige). 2007. URL:
  • 130
    Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E, Hynan LS, et al, for the Acute Liver Failure Study Group. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology 2005; 42: 136472.
  • 131
    Alanko K, Stubb S, Kauppinen K. Cutaneous drug reactions: clinical types and causative agents. A five-year survey of in-patients (1981-1985). Acta Derm Venereol 1989; 69: 2236.
  • 132
    US Food and Drug Administration. Alert for healthcare professionals: Valdecoxib (marketed as Bextra). 2005. URL:
  • 133
    Lang BA, Finlayson LA. Naproxen-induced pseudoporphyria in patients with juvenile rheumatoid arthritis. J Pediatr 1994; 124: 63942.
  • 134
    Schad SG, Kraus A, Haubitz I, Trcka J, Hamm H, Girschick HJ. Early onset pauciarticular arthritis is the major risk factor for naproxen-induced pseudoporphyria in juvenile idiopathic arthritis. Arthritis Res Ther 2007; 9: R10.
  • 135
    Woessner KM, Simon RA, Stevenson DD. The safety of celecoxib in patients with aspirin-sensitive asthma. Arthritis Rheum 2002; 46: 22016.
  • 136
    Szczeklik A, Nizankowska E, Bochenek G, Nagraba K, Mejza F, Swierczynska M. Safety of a specific COX-2 inhibitor in aspirin-induced asthma. Clin Exp Allergy 2000; 31: 21925.
  • 137
    Dahlen B, Szczeklik A, Murray JJ, for the Celecoxib in Aspirin-Intolerant Asthma Study Group. Celecoxib in patients with asthma and aspirin intolerance [letter]. New Engl J Med 2001; 344: 142.
  • 138
    Stevenson DD, Simon RA. Lack of cross-reactivity between rofecoxib and aspirin in aspirin-sensitive patients with asthma. J Allergy Clin Immunol 2001; 108: 4751.
  • 139
    Ibanez L, Vidal X, Ballarin E, Laporte JR. Population-based drug-induced agranulocytosis. Arch Intern Med 2005; 165: 86974.
  • 140
    O'Brien WM, Bagby GF. Rare adverse reactions to nonsteroidal antiinflammatory drugs: 4. J Rheumatol 1985; 12: 78590.
  • 141
    Hoppmann RA, Peden JG, Ober SK. Central nervous system side effects of nonsteroidal anti-inflammatory drugs: aseptic meningitis, psychosis, and cognitive dysfunction. Arch Intern Med 1991; 151: 130913.
  • 142
    Bradford WD, Kleit AN, Nietert PJ, Steyer T, McIlwain T, Ornstein S. How direct-to-consumer television advertising for osteoarthritis drugs affects physicians' prescribing behavior. Health Aff (Millwood) 2006; 25: 13717.
  • 143
    Curhan GC, Bullock AJ, Hankinson SE, Willett WC, Speizer FE, Stampfer MJ. Frequency of use of acetaminophen, nonsteroidal anti-inflammatory drugs, and aspirin in US women. Pharmacoepidemiol Drug Saf 2002; 11: 68793.
  • 144
    Richardson CG, Chalmers A, Llewellyn-Thomas HA, Klinkhoff A, Carswell A, Kopec JA. Pain relief in osteoarthritis: patients' willingness to risk medication-induced gastrointestinal, cardiovascular, and cerebrovascular complications. J Rheumatol 2007; 34: 156975.
  • 145
    Solomon DH, Glynn RJ, Bohn R, Levin S, Avorn J. The hidden cost of nonselective nonsteroidal antiinflammatory drugs in older patients. J Rheumatol 2003; 30: 7928.
  • 146
    Dai C, Stafford RS, Alexander GC. National trends in cyclooxygenase-2 inhibitor use since market release: nonselective diffusion of a selectively cost-effective innovation. Arch Intern Med 2005; 165: 1717.
  • 147
    Patino FG, Allison J, Olivieri J, Mudano A, Juarez L, Person S, et al. The effects of physician specialty and patient comorbidities on the use and discontinuation of coxibs. Arthritis Rheum 2003; 49: 2939.
  • 148
    Greenberg JD, Bingham CO III, Abramson SB, Reed G, Sebaldt RJ, Kremer J. Effect of cardiovascular comorbidities and concomitant aspirin use on selection of cyclooxygenase inhibitor among rheumatologists. Arthritis Rheum 2005; 53: 127.
  • 149
    Smalley W, Stein CM, Arbogast PG, Eisen G, Ray WA, Griffin M. Underutilization of gastroprotective measures in patients receiving nonsteroidal antiinflammatory drugs. Arthritis Rheum 2002; 46: 2195200.
  • 150
    MacLean CH, Saag KG, Solomon DH, Morton SC, Sampsel S, Klippel JH. Measuring quality in arthritis care: methods for developing the Arthritis Foundation's quality indicator set. Arthritis Rheum 2004; 51: 193202.
  • 151
    Spiegel BM, Targownik L, Dulai GS, Gralnek IM. The cost-effectiveness of cyclooxygenase-2 selective inhibitors in the management of chronic arthritis. Ann Intern Med 2003; 138: 795806.
  • 152
    Maetzel A, Krahn M, Naglie G. The cost effectiveness of rofecoxib and celecoxib in patients with osteoarthritis or rheumatoid arthritis. Arthritis Rheum 2003; 49: 28392.
  • 153
    Choi HK, Seeger JD, Kuntz KM. Effects of rofecoxib and naproxen on life expectancy among patients with rheumatoid arthritis: a decision analysis. Am J Med 2004; 116: 6219.
  • 154
    Strand V. Are COX-2 inhibitors preferable to non-selective non-steroidal anti-inflammatory drugs in patients with risk of cardiovascular events taking low-dose aspirin? Lancet 2007; 370: 213851.