• 1
    National Institutes of Health. Use of non-steroidal anti-inflammatory drugs suspended in large Alzheimer's disease prevention trial. URL:
  • 2
    Schafer AI. Effects of nonsteroidal anti-inflammatory drugs on platelet function and systemic hemostasis. J Clin Pharmacol 1995; 35: 20919.
  • 3
    McAdam BF, Catella-Lawson F, Mardini IA, Kapoor S, Lawson JA, Fitzgerald GA. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sci U S A 1999; 96: 2727.
  • 4
    Topper JN, Cai J, Falb D, Gimbrone MA Jr. Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. Proc Natl Acad Sci U S A 1996; 93: 1041722.
  • 5
    FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2 [review]. N Engl J Med 2001; 345: 43342.
  • 6
    Crofford LJ, Oates JC, McCune WJ, Gupta S, Kaplan MJ, Catella-Lawson F, et al. Thrombosis in patients with connective tissue diseases treated with specific cyclooxygenase 2 inhibitors: a report of four cases. Arthritis Rheum 2000; 43: 18916.
  • 7
    Cheng Y, Austin SC, Rocca B, Koller BH, Coffman TM, Grosser T, et al. Role of prostacyclin in the cardiovascular response to thromboxane A2. Science 2002; 296: 53941.
  • 8
    Egan KM, Lawson JA, Fries S, Koller B, Rader DJ, Smyth EM, et al. COX-2-derived prostacyclin confers atheroprotection on female mice. Science 2004; 306: 19547.
  • 9
    FitzGerald G. Mechanism based adverse cardiovascular events and specific inhibitors of COX-2. URL:
  • 10
    Kuvin JT, Patel AR, Sliney KA, Pandian NG, Rand WM, Udelson JE, et al. Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease. J Am Coll Cardiol 2001; 38: 18439.
  • 11
    Chenevard R, Hurlimann D, Bechir M, Enseleit F, Spieker L, Hermann M, et al. Selective COX-2 inhibition improves endothelial function in coronary artery disease. Circulation 2003; 107: 4059.
  • 12
    Widlansky ME, Price DT, Gokce N, Eberhardt RT, Duffy SJ, Holbrook M, et al. Short- and long-term COX-2 inhibition reverses endothelial dysfunction in patients with hypertension. Hypertension 2003; 42: 3105.
  • 13
    Title LM, Giddens K, McInerney MM, McQuenn MJ, Nassar BA. Effect of cyclooxygenase-2 inhibition with rofecoxib on endothelial dysfunction and inflammatory markers in patients with coronary artery disease. J Am Coll Cardiol 2003; 42: 174753.
  • 14
    Bogaty P, Brophy JM, Noel M, Boyer L, Simard S, Bertrand F, et al. Impact of prolonged cyclooxygenase-2 inhibition on inflammatory markers and endothelial function in patients with inschmeic heart disease and raised C-reactive protein. Circulation 2004; 110: 9349.
  • 15
    Gurwitz JH, Avorn J, Bohn RL, Glynn RJ, Monane M, Mogun H. Initiation of antihypertensive treatment during nonsteroidal anti-inflammatory drug therapy. JAMA 1994; 272: 7816.
  • 16
    Pope JE, Anderson JJ, Felson DT. A meta-analysis of the effects of nonsteroidal anti-inflammatory drugs on blood pressure. Arch Intern Med 1993; 153: 47784.
  • 17
    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.
  • 18
    Walter MF, Jacob RF, Day CA, Dahlborg R, Weng Y, Mason RP. Sulfone COX-2 inhibitors increase susceptibility of human LDL and plasma to oxidative modification: comparison to sulfonamide COX-2 inhibitors and NSAIDs. Atherosclerosis 2004; 177: 23543.
  • 19
    Strand V, Hochberg MC. The risk of cardiovascular thrombotic events with selective cyclcooxygenase-2 inhibitors. Arthritis Rheum 2002; 47: 34955.
  • 20
    Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al, and the VIGOR Study Group. VIGOR Study Group: comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med 2000; 343: 15208.
  • 21
    FDA. Assessing risk/benefit of rofecoxib/coxibs. URL:
  • 22
    Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, et al, and the Adenomatous Polyp Prevention on Vioxx (APPROVe) Trial Investigations. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 2005; 352: 1092102.
  • 23
    Weir MR, Sperling RS, Reicin A, Gertz BJ. Selective COX-2 inhibition and cardiovascular effects: a review of the rofecoxib development program. Am Heart J 2003; 146: 591604.
  • 24
    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.
  • 25
    FitzGerald GA. COX-2 and beyond: approaches to prostaglandin inhibition in human disease. Nat Rev Drug Discov 2003; 2: 87990.
  • 26
    Solomon SD, McMurray JV, Pfeffer MA, Wittes J, Fowler R, Finn P, et al, and the Adenoma Prevention with Celecoxib (APC) Study Investigators. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005; 352: 107180.
  • 27
    Farkouh ME, Kirshner H, Harrington, RA, Ruland S, Verheugt FW, Schnitzer TJ, et al, and the TARGET Study Group. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes, randomised controlled trial. Lancet 2004; 364: 67584.
  • 28
    FDA. Cardiovascular safety and risk-benefit assessment. URL:
  • 29
    Ott E, Nussmeier NA, Duke PC, Feneck RO, Alston RP, Snabes MC, et al, and the Multicenter Study of Perioperative Ischemia (McSPI) Research Group, and the Ischemia Research and Education Foundation (IREF) Investigators. Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. J Thoracic Cardiovasc Surg 2003; 125: 148192.
  • 30
    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.
  • 31
    Ray WA, Stein CM, Daugherty JR, Hall K, Arbogast PG, Griffin MR. COX-2 selective nonsteroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet 2002; 360: 10713.
  • 32
    Solomon DH, Schneeweiss S, Glynn RJ, Kiyota Y, Levin R, Mogun H, et al. Relationship between selective COX-2 inhibitors and acute myocardial infarction. Circulation 2004; 109: 206873.
  • 33
    Schneeweiss S, Glynn RJ, Tsai EH, Avorn J, Solomon DH. Adjusting for unmeasured confounders in pharmacoepidemiologic claims data using external information: the example of COX-2 inhibitiors and myocardial infarction. Epidemiology 2005; 16: 1724.
  • 34
    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.
  • 35
    Kimmel SE, Berlin JA, Reilly M, Jaskowiak J, Kishel L, Chittams J, et al. Patients exposed to rofecoxib and celecoxib have different odds of nonfatal myocardial infarction. Ann Intern Med 2005; 142: 15764.
  • 36
    Mamdani M, Rochon P, Juurlink DN, Anderson GM, Kopp A, Naglie G, et al. Effect of selective cyclooxygenase 2 inhibitors and naproxen on short-term risk of acute myocardial infarction. Arch Intern Med 2003; 163: 4816.
  • 37
    Shaya FT, Blume SW, Blanchette CM, Weir MR, Mullins CD. Selective cyclooxygenase-2 inhibition and cardiovascular effects. Arch Intern Med 2005; 165: 1816.
  • 38
    Suissa S. Study designs and databases available for pharmacoepidemiology studies. American College of Rheumatology 68th Annual Scientific Meeting; 2004 Oct 16–21; San Antonio, TX.
  • 39
    Ray WA. Evaluating medication effects outside of clinical trials: new user designs. Am J Epidemiol 2003; 158: 91520.
  • 40
    Moses PL, Schroeder B, Alkhatib O, Ferrentino N, Suppan T, Lidofsky SD. Severe hepatotoxicity associated with bromfenac sodium. Am J Gastroenterol 1999; 94: 13936.
    Direct Link:
  • 41
    Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, la Grenade L, et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA 2004; 292: 258590.
  • 42
    Brenner SS, Herrlinger C, Dilger K, Murdter TE, Hofmann U, Marx C, et al. Influence of age and cytochrome P450 2C9 genotype on the steady-state disposition of diclofenac and celecoxib. ClinPharmacokinet 2003; 42: 28392.
  • 43
    Lloyd-James DM, Wilson PW, Larson MG, Beiser A, Leip EP, D'Agostino RB, et al. Framingham risk score and prediction of lifetime risk for coronary heart disease. Am J Cardiol 2004; 94: 204.
  • 44
    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.
  • 45
    Fries JF, Murtagh KN, Bennett M, Zatarain E, Lingala B, Bruce B. The rise and decline in nonsteroidal antiinflammatory drug–associated gastropathy in rheumatoid arthritis. Arthritis Rheum 2004; 50: 243340.
  • 46
    Singh G, Ramey DR. NSAID induced gastrointestinal complications: the ARAMIS perspective: 1997. J Rheumatol 1998; 25 Suppl 51: 816.