Problems of cardiovascular toxicity of coxibs and non-selective NSA


Authors: Š. Forejtová
Authors‘ workplace: Revmatologický ústav, Praha, ředitel prof. MUDr. Karel Pavelka, DrSc.
Published in: Vnitř Lék 2006; 52(7-8): 677-685
Category: 130th Internal Medicine Day - Rheumatology in clinical practice

Overview

Non-steroidal antirheumatics (NSA) belong to the most often prescribed drugs. Certain observation studies indicate that they are used by 20 to 30% of population of developed countries. The most common NSA’s adverse effects are gastrointestinal complications. Coxibs have been developed as an alternative to conventional non-selective NSA; with similar efficacy, they should reduce the risk of development of gastrointestinal complications. In the few last years, possible toxicity of coxibs and other non-steroidal antirheumatics has been widely discussed. The VIGOR study, which was performed 6 years ago, showed five times higher incidence of nonfatal myocardial infarction in patients with rofecoxib therapy as compared with naproxen. Afterwards, there was much debate about rofecoxib, and coxibs in general, whose cardiotoxicity was supported and confuted at the same time. Possible cardioprotective effect of naproxen was discussed too. Later on, results of the APPROVE study (Adenoma Polyp Prevention on Vioxx) made Merck & Co., Inc. withdraw rofecoxib from all markets voluntarily. In the end of 2004, three controversial studies on celecoxib were published. Although the first study (Adenoma Prevention with Celecoxib study, APC) showed higher cardiovascular risk of celecoxib, the second study (Prevention of Adenomatosus Polyps, PreSAP) did not verify these results. Surprisingly, the third study (Alzheimer Disease and Prevention Trial, ADAPT) proved 50% increase of the risk of cardiovascular (CV) toxicity of naproxen. In the last year, researchers have tried to decide whether CV toxicity is a class effect of coxib group or a class effect of all NSA. Many observation studies proved higher CV risk both of coxibs (particularly rofecoxib) and non-selective NSA including naproxen. These new findings moved the American FDA (Food and Drug Administration) to publish guidance concerning higher CV risk of all coxibs and NSA. For the time being, the EMEA (European Agency for Evaluation of Medicinal Products) does not change its attitude to NSA; coxibs are contraindicated in patients with ischemic heart disease, cerebrovascular disease and peripheral artery disease; they should be used with caution in high-risk patients. Final assessment of the problems of CV toxicity of NSA and coxibs will be a case of a long-term randomized study focused on the incidence of cardiovascular adverse effects.

Key words:
non-steroidal antirheumatics – coxibs – myocardial infarction


Sources

1. Talley NJ, Evans JM, Fleming KC et al. Nonsteroidal antiinflammatory drug and dyspepsia in the elderly. Dig Dis Sci 1995; 40: 1345-1350.

2. Laine L. Nonsteroidal anti-inflammatory drug gastropathy. Gastrointest Endosc Clin N Am 1996; 6: 489-504.

3. Langman MJ, Weil J, Wainwright P et al. Risk of bleeding peptic ulcer associated with individual nonsteroidal antiinflammatory drugs. Lancet 1994: 343: 1075-1078.

4. Allison MC, Howatson AG, Torrance CJ et al. Gastrointestinal damage associated with the use of non-steroidal anti-inflammatory drugs. N Engl J Med 1992; 327: 749-754.

5. Fries JF, Miller SP, Spitz PW et al. Toward an epidemiology of gastropathy associated with nonsteroidal antirevmatic drug use. Gastroenterology 1989; Suppl: 647-655.

6. Rahme E, Marentette MA, Kong SX et al. Use of NSAIDs, COX-2 inhibitors, and acetaminophen and associated coprescriptions of gastroprotective agents in an elderly population. Arthritis Rheum 2002; 47: 595-602.

7. Bombardier C, Laine L, Reicin A et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000; 343: 1520-1528.

8. Silverstein FE, Faich G, Goldstein JL et al. Gastointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis; the CLASS study: a randomized controlled trial. Celecoxib long-therm artrhritis safety study. JAMA 2000; 284: 1247-1255.

9. Singh G, Fort JG, Goldstein JL et al. Celecoxib versus aproxen and diclofenac in osteoarthritis patients. SUCCESS-1 study. Am J Med 2006; 119: 255-266.

10. Bresalier RS, Sandler RA, Quan H et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl.J Med 2005; 352: 1092-1102.

11. Jüni P, Reichenbach S, Sterchi R et al. Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet 2004; 364: 2021-2029.

12. Solomon SD, McMurray J, Pfeffer MA et al. Cardiovascular events associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005; 352: 1071-1080.

13. Farkouh ME, Kirshner H, Harrington RA et al. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised centrolled trial. Lancet 2004; 364: 675-684.

14. White WB, Strand V, Roberts R et al. Effect of the cyclooxygenase-2 specific inhibitor valdecoxib versus nonsteroidal antiinflammatory agents and placebo on cardiovascular trombotic events in patients with arthritis. Am J Ther 2004; 11: 244-250.

15. Ott E, Nussmeier NA, Duke PC et al. Efficacy and safety of the cyclooxygense 2 inhibitors parekoxib and valdekoxib in patiens undergoing coronary artery bypass surgery. J Thorac Cardiovasc Surgery 2003; 125: 1481-1492.

16. Konstam MA, Weir MR, Reicin A et al. Cardiovascular thrombotic events in controlled clinical trials of rofekoxib. Circulation 2001; 104: 2280-2288.

17. Mukherjee D, Nissen SE, Topol EJ et al. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 2001; 286: 954-959.

18. Ray WA, Stein CM, Daugherty JR et al. COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary hearth disease. Lancet 2002; 360: 1071-1073.

19. Mamdani M, Rochon P, Juurlink DN et al. Effect of selective cyclooxygenase 2 inhibitor and naproxen on short-term risk of acute myocardial infarction in the elderly. Arch Intern Med 2003; 24: 481-486.

20. Solomon DH, Schneeweiss S, Glynn RJ et al. Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation 2004; 109: 2068-2073.

21. Kimmel SE, Berlin JA, Reilly M et al. Patients exposed to rofecoxib and celecoxib have different odds of nonfatal myocardial infarction. Ann Intern Med 2005; 142: 157-164.

22. Garcia Rodriquez LA, Varas C, Patrono C. Differential effects of aspirin and non-steroidal antiinflammatory drugs in the primary prevention od myocyrdial infarction in post-menopausal women. Epidemiology 2000; 11: 382-387.

23. Solomon DH, Glynn RJ, Levin R et al. Nonsteroidal anti-inflammatory drug use and acute myocardial infarction. Arch Intern Med 2002; 162: 1099-1104.

24. Watson DJ, Rhodes T, Cai B et al. Lower risk of tromboembolic cardiovascular events with naproxen among patients with rheumatoid arthritis. Arch Intern Med 2002; 162: 1105-1110.

25. Rahme W, Pilote L, LeLorier J. Association between naproxen use and protection against acute myocardial infarction. Arch Intern Med 2002; 162: 1111-1115.

26. Ray WA, Stein CM, Hall K et al. Nonsteroidal anti-inflammatory drugs and risk of serious coronary heart disease: an observational cohort study. Lancet 2002; 359: 118-123.

27. Graham DJ, Campen D, Hui R et al. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclooxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet 2005; 365: 475-481.

28. Sudbø J, Lee JJ, Lippman SM et al. Non-steroidal anti-inflammatori drugs and risk of oral cancer: a nested case-control study. Lancet 2005; 366: 1355-1366.

29. Shaya FT, Blume SW, Blanchette CM et al. Selective cyclooxygenase-2 inhibition and cardiovascular effects. Arch Intern Med 2005; 165: 181-186.

30. Hippisley-Cox J, Coupland C. Risk of myocardial infarction in patients taking cyclooxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case control analysis. BMJ 2005; 330: 1366-1369.

31. Lévesque LE, Brlohy JM, Zhang B. The risk for myocardial infarction with cyclooxygenase-2 inhibitors: a population study of elderly adults. Ann Intern Med 2005; 142: 481-489.

32. Johnsen A, Larsson H, Tarone R et al. Risk of hospitalization for myocardial infarction aminy users of Rofecoxib, Celecoxib, and other NSAIDs. Arch Intern Med 2005; 165: 978-984.

33. Whelton A, Fort JG, Puma JA et al. Cyclooxygenase-2 specific inhibitors and cardioreanl function: a randomized, controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients. Am J Ther 2001; 8: 85-95.

34. Whelton A, White WB, Bello AE et al. Effects of celecoxib and rofekoxib on blood pressure and edema in patients ≥ 65 years of age with systemic hypertension and osteoarthritis. Am J Cardiol 2002; 90: 959-963.

35. White WB, Kent J, Tailor A et al. Effects of celecoxib on ambulatory blood pressure in hypertensive patients on ACE inhibitors. Hypertension 2002; 39: 929-934.

36. Mamdani M, Juurlink DN, Lee DS et al. Cyclooxygenase-2 inhibitors versus non-selective non-steroidal anti-inflammatory drugs and congestive heart failure outcomes in elderly patients: a population-based cohort study. Lancet 2004; 363: 1751-1756.

37. Hudson M, Hugues R, Pilote L. Differences in outcomes of patients with congestive heart failure precribed celecoxib, rofecoxib, or non-steroidal anti-inflammatory drug: population based study. BMJ 2005; 330: 1365-1370.

38. Johnson AG, Nguyen TV, Ray RO. Do nonsteroidal antiinflammatory drugs affect blood pressure? A metaanalysis. Ann Intern Med 1994; 121: 289-300.

39. Van den Hoogen PC, Feskens EJ, Nagelkerke NJ et al. The relation between blood pressure and mortality due to coronary heart disease among men in different parts of the world. Seven Countries Study Research Group. N Engl J Med 2000; 342: 1-8.

40. Prevention of stroke by anti-hypertensive drug treatment in old persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991; 265: 3255-3264.

41. Steassen JA, Wang JG, Thijs L. Cardiovascular prevention and blood pressure reduction: a metaanalysis. Lancet 2001; 358: 1305-1315.

42. Breyer MD, Breyer RM. Prostaglandin E receptors and the kidney. Am J Renal Physiol 2000; 279 (Suppl F): F12-F23.

43. Kammerl MC, Nusing RM, Richthammer W et al. Inhibition of COX-2 counteracts the effects of diuretics in rats. Kidney Intern 2001; 60: 1684-1691.

44. Horackova M, Schűck O, Komers R et al. Effect of rofecoxib on the glomerular filtration rate, proteinuria and the renin-angiotensin-aldosterone systém in elderly subjects with chronic renal impairment. Int J Clin Pharmacol Ther Toxicol 2005; 43: 413-419.

45. Harris RC. Cyclooxygenase-2 inhibition and renal physiology. Am J Cardiol 2002; 89 (Suppl D): 10D-17D.

46. Zhang MZ, Harris RC, Mc Kanna JA. Regulation of cyclooxygenase-2 (COX-2) in rat renal cortex by adrenal glucocorticoids and mineralocorticoids. Proc Nat Acad Sci USA 1999; 96: 15280-15285.

47. De Maria AN, Weir MR. Coxibs-beyond the GI tract: renal and cardiovascular issues. J Pain Symptom Manage 2003; 25S: S41-S49.

48. Solomon DH, Schneeweiss S, Levin R et al. Relationship. between COX-2 specific inhibitors and hypertension. Hypertension 2004; 44: 1-6.

49. Whelton A, Fort JG, Puma JA et al. Cyclooxygenase-2 specific inhibitors and cardiorenal function: a randomized, controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients. Am J Ther 2001; 8: 85-95.

50. Cho J, Cooke C, Proveaux W. A retrospective review of the effect of COX-2 inhibitors on blood pressure change. Am J Ther 2003; 10: 311-317.

51. Sowers JR et al. The effects of cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory therapy on 24-hour blood pressure in patients with hypertension, osteoarthritis and type 2 diabetes mellitus. Arch Intern Med 2005; 165: 161-168.

52. Aw TJ, Haas SJ, Liew D et al. Meta-analysis of cyclooxygenase-2 inhibitors and teir effects on blood pressure. Ann Intern Med 2005; 165: 490-496.

53. Catella-Lawson F, Reilly MP, Kapoor SC et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med 2001; 345: 1809-1817.

54. MacDonald TM, Wei L. Effect of ibuprofen on cardioprotective effect of aspirin. Lancet 2003; 361: 573-574.

55. Kurth T, Glynn RJ, Walker AM et al. Inhibition of clinical benefits of aspirin on first myocardial infarction by nonsteroidal antiinflammatory drugs. Circulation 2003; 108: 1191-1195.

56. Hudson M, Baron M, Rahme E et al. Ibuprofen may abrogate the benefits of aspirin when used for secondary prevention of myocardial infarction. J Rheumatol 2005; 32: 1589-1593.

57. Wilner KD, Rushing M, Walden C et al. Celecoxib does no affect the antiplatelet activity of aspirin in healthy volunteers. J Clin Pharmacol 2002; 42: 1027-1030.

58. Capone ML, Sciulli MG, Toconelli S et al. Pharmacodynamic interaction of naproxen with low-dose aspirin in healthy subjects. J Am Coll Cardiol 2005; 45: 1295-1301.

59. Walter MF, Jacob RF, Day CA et al. 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: 235-243.

60. Chenevard R, Hűrlmann D, Ruschitzka F et al. Selective COX-2 inhibition improves endotelial function in coronary artery disease. Circulation 2003; 107: 405-409.

61. Widlanski ME, Price DT, Vita JA et al. Short- and long-term COX-2 inhibition reverses endotelial dysfunktion in patients with hypertension. Hypertension 2003; 42: 310-315.

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