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Colorectal cancer is an important burden on the U.S. population. The use of NSAID chemoprophylaxis, alone or in combination with a recommended screening program, is 1 strategy to reduce the incidence of colorectal adenomas, CRC, and CRC-related death.

The results of our systematic review suggest that the use of non-ASA NSAIDs for CRC chemoprevention is effective at reducing the incidence of colorectal adenomas and CRC. Cyclooxygenase-2 inhibitors seem to be effective at reducing the incidence of colorectal adenoma in patients with previous adenomatous polyps. Higher doses and longer durations of use of non-ASA NSAIDs seem to be associated with greater protection from CRC and adenomas. We found the magnitude of the relative risk reduction for CRC incidence to be approximately 30% to 40% in the pooled analyses.

We found no observational data on the effect of COX-2 inhibitors on CRC incidence or CRC-related death, although a single cohort study showed no effect of the non-ASA NSAID ibuprofen on CRC death but demonstrated a small statistically significant increase in allcause mortality.21 Further, no RCT data exist on CRC incidence with the long-term use of COX-2 inhibitors or non-ASA NSAIDs that are similar to data from the ASA-based Physicians' and Women's Health studies.9,10

The use of non-ASA NSAIDs and COX-2 inhibitors are each associated with important harms. Non-ASA NSAIDs are associated with an increased risk for ulcers and clinically important ulcer complications, such as hemorrhage, perforation, or pyloric obstruction. Cyclooxygenase-2 inhibitors are associated with fewer gastrointestinal symptoms, endoscopic ulcers, and clinically important ulcer complications than non-ASA NSAIDs. However, data from the APPROVe study18 demonstrated that over a 3-year period, COX-2 inhibitors were associated with a statistically significant increased risk for clinical ulcer complications compared with placebo.18 Although these data are in keeping with improved gastrointestinal safety of COX-2 inhibitors over non-ASA NSAIDs, the gastrointestinal safety of COX-2 inhibitors is not equivalent to that seen with placebo, as has been suggested in the past. On the other hand, COX-2 inhibitors are associated with an increased risk for adverse cardiovascular outcomes.56

During the conduct of our systematic review, rofecoxib was withdrawn from the market because of the results of the polyp prevention APPROVe study,78 which demonstrated an excess risk for cardiovascular events (16 per 1000 events) with the use of rofecoxib, confirming the suspicions reported by the VIGOR investigators.76 Subsequently, celecoxib was also found to have an excess risk for cardiovascular events (13 to 21 per 1000 events) in another polyp prevention study (Adenoma Prevention with Celecoxib [APC]).79 Valdecoxib was also withdrawn because of excess risk for cardiovascular events in 2 short-term cardiac surgery pain studies (Coronary Artery Bypass Graft [CABG] 1 and 2) and because of a rare dermatologic toxicity.80,81

A systematic review of the cardiovascular harms of rofecoxib and non-ASA NSAIDs59 suggested a small cardiovascular protective effect of naproxen, although the included studies were heterogeneous. Naproxen's relatively long half-life of 14 hours makes a twice-daily dosing schedule theoretically capable of consistently blocking COX-1 and potentially providing some degree of cardioprotection. Clinical trial data of the quality comparable to data available for the COX-2 inhibitors is not available for non-ASA NSAIDs. However, a recent meta-analysis56 using an extensive set of RCT data derived from published and unpublished studies suggests that, as a group, COX-2 inhibitors are associated with an increased risk for adverse cardiovascular outcomes (predominantly MI) when compared with placebo or naproxen but not when compared with nonnaproxen, non-ASA NSAIDs. These data, and evidence from some population-based studies,82-84 suggest that the increased risk for cardiovascular harms with COX-2 inhibitors is shared by nonnaproxen, non-ASA NSAIDs (higher doses of ibuprofen and diclofenac).56

Although it is tempting to consider adding ASA to a COX-2 inhibitor for cardioprotection, there seems to be an attenuation of the gastrointestinal safety of COX-2 inhibitors with this strategy. However, it should be noted that these observations were derived from post hoc subgroup analyses.

Non-ASA NSAIDs and COX-2 inhibitors are used for longer durations for a variety of arthritic and inflammatory conditions.12 Although their use for these conditions is more easily justified, it is much more difficult to make a case for their use for the chemoprevention of adenomas and CRC in average-risk individuals or even in individuals with a history of polyps. In light of the cardiovascular and gastrointestinal toxicity of these agents when used in a multiyear setting, the demonstration of the chemopreventive efficacy may be a "pyrrhic victory" as stated by Lynch85 in his editorial on the APPROVe trial. Furthermore, considering the newly identified risks for cardiovascular events associated with these agents, the cost-effectiveness of a chemopreventive strategy for CRC needs to be fully evaluated, particularly because a screening strategy alone appears to be effective.4 In a simplified risk-benefit analysis, assuming that CRC incidence can be reduced by 50% with COX-2 inhibitor use, Psaty and Potter86 suggested that significantly more cardiovascular events would occur than cases of CRC prevented. However, the balance of benefits and risks in high-risk patients, such as those with familial adenomatous polyposis and nonpolyposis syndromes and those with a history of CRC, may be quite different from that detailed here for average- to higher-risk individuals. A role for COX-2 inhibitors continues to be evaluated in the setting of these high-risk patients.86

Although ASA seems to be an attractive candidate for CRC chemoprophylaxis, the apparent need for doses higher than that used for cardiovascular protection represents a crucial drawback.48 Likewise, the improved gastrointestinal safety profile of COX-2 inhibitors over non-ASA NSAIDs made COX-2 inhibitors an attractive candidate until their cardiovascular toxicity came to light. Nonnaproxen, non-ASA NSAIDs seem to be the least attractive option because they are associated with both gastrointestinal and cardiovascular toxicity.

In conclusion, non-ASA NSAIDs seem to be effective at reducing the incidence of colorectal adenomas and CRC in observational studies. Good-quality RCT data suggest that COX-2 inhibitors are effective at reducing the incidence of colorectal adenomas in patients with previous adenomas. However, positive data on the reduction of death is lacking for both non-ASA NSAIDs and COX-2 inhibitors.

No quantitative data exist on the risk for gastrointestinal or cardiovascular harms associated with daily, multiyear use of non-ASA NSAIDs. Available data on COX-2 inhibitors suggest that absolute risk increases of over 1% for cardiovascular events and for clinically important gastrointestinal complications can be anticipated after only 2 to 3 years of use, and higher risks may accrue over longer periods. Furthermore, the cost-effectiveness of chemoprevention needs to be considered carefully and compared with other strategies, such as colorectal cancer screening alone. Therefore, the balance of benefits and risks does not appear to favor chemoprevention with non-ASA NSAIDs or COX-2 inhibitors in average-risk individuals or in those with a history of colorectal adenomas.

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1. Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, et al. Cancer statistics, 2004. CA Cancer J Clin 2004;54:8-29. [PMID: 14974761]

2. Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, et al. Cancer statistics, 2006. CA Cancer J Clin 2006;56:106-30. [PMID: 16514137]

3. Hayden M, Pignone M, Phillips C, Mulrow C. Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002;136:161-72. [PMID: 11790072]

4. Thiis-Evensen E, Hoff GS, Sauar J, Langmark F, Majak BM, Vatn MH. Population-based surveillance by colonoscopy: effect on the incidence of colorectal cancer. Telemark Polyp Study I. Scand J Gastroenterol 1999;34:414-20. [PMID: 10365903]

5. Centers for Disease Control and Prevention. Trends in screening for colorectal cancer—United States, 1997 and 1999. MMWR Morb Mortal Wkly Rep 2001;50:162-6. [PMID: 11393486]

6. Centers for Disease Control and Prevention. Trends in screening for colorectal cancer—United States, 1997 and 1999. JAMA 2001;285:1570-1. [PMID: 11302136]

7. Centers for Disease Control and Prevention. Colorectal cancer test use among persons aged > or = 50 years—United States, 2001. MMWR Morb Mortal Wkly Rep 2003;52:193-6. [PMID: 12653456]

8. Seeff LC, Nadel MR, Klabunde CN, Thompson T, Shapiro JA, Vernon SW, et al. Patterns and predictors of colorectal cancer test use in the adult U.S. population. Cancer 2004;100:2093-103. [PMID: 15139050]

9. Gann PH, Manson JE, Glynn RJ, Buring JE, Hennekens CH. Low-dose aspirin and incidence of colorectal tumors in a randomized trial. J Natl Cancer Inst 1993;85:1220-4. [PMID: 8331682]

10. Cook NR, Lee IM, Gaziano JM, Gordon D, Ridker PM, Manson JE, et al. Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial. JAMA 2005;294:47-55. [PMID: 15998890]

11. Rostom A, Dube´ C, Lewin G, Tsertsvadze A, Barrowman N, Code C, et al. Use of aspirin and NSAIDs to prevent colorectal cancer. Evidence synthesis prepared by the University of Ottawa Evidence-based Practice Center under contract no. 290-02-0021. Rockville, MD: Agency for Healthcare Research and Quality; 2006.

12. Rostom A, Dube´ C, Jolicoeur E, Boucher M, Joyce J. Gastroduodenal ulcers associated with the use of non-steroidal anti-inflammatory drugs: a systematic review of preventative pharmacological interventions. Ottawa, Canada: Canadian Coordinating Office for Health Technology Assessment; 2004. Technology report no. 38.

13. Rostom A, Dube C, Wells G, Tugwell P, Welch V, Jolicoeur E, et al. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev 2002:CD002296. [PMID: 12519573]

14. Asano TK, McLeod RS. Non steroidal anti-inflammatory drugs (NSAID) and Aspirin for preventing colorectal adenomas and carcinomas. Cochrane Database Syst Rev 2004:CD004079. [PMID: 15106236]

15. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60. [PMID: 12958120]

16. Paganini-Hill A. Aspirin and colorectal cancer: the Leisure World cohort revisited. Prev Med 1995;24:113-5. [PMID: 7597009]

17. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88. [PMID: 3802833]

18. Baron JA, Sandler RS, Bresalier RS, Quan H, Riddell R, Lanas A, et al. A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas. Gastroenterology 2006;131:1674-82. [PMID: 17087947]

19. Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K. et al. Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med 2006;355:873-84. [PMID: 16943400]

20. Arber N, Eagle CJ, Spicak J, Racz I, Dite P, Hajer J, et al. Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med 2006;355:885-95. [PMID: 16943401]

21. Lipworth L, Friis S, Blot WJ, McLaughlin JK, Mellemkjaer L, Johnsen SP, et al. A population-based cohort study of mortality among users of ibuprofen in Denmark. Am J Ther 2004;11:156-63. [PMID: 15133529]

22. García-Rodríguez LA, Huerta-Alvarez C. Reduced risk of colorectal cancer among long-term users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs. Epidemiology 2001;12:88-93. [PMID: 11138826]

23. Kune GA, Kune S, Watson LF. Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study. Cancer Res 1988;48:4399-404. [PMID: 3390835]

24. Juarranz M, Calle-Puro´n ME, González-Navarro A, Regidor-Poyatos E, Soriano T, Martínez-Hernandez D, et al. Physical exercise, use of Plantago ovata and aspirin, and reduced risk of colon cancer. Eur J Cancer Prev 2002;11:465-72. [PMID: 12394244]

25. Reeves MJ, Newcomb PA, Trentham-Dietz A, Storer BE, Remington PL. Nonsteroidal anti-inflammatory drug use and protection against colorectal cancer in women. Cancer Epidemiol Biomarkers Prev 1996;5:955-60. [PMID: 8959316]

26. Slattery ML, Samowitz W, Hoffman M, Ma KN, Levin TR, Neuhausen S. Aspirin, NSAIDs, and colorectal cancer: possible involvement in an insulin-related pathway. Cancer Epidemiol Biomarkers Prev 2004;13:538-45. [PMID: 15066917]

27. Muscat JE, Stellman SD, Wynder EL. Nonsteroidal antiinflammatory drugs and colorectal cancer. Cancer 1994;74:1847-54. [PMID: 8082089]

28. Shaheen NJ, Silverman LM, Keku T, Lawrence LB, Rohlfs EM, Martin CF, et al. Association between hemochromatosis (HFE) gene mutation carrier status and the risk of colon cancer. J Natl Cancer Inst 2003;95:154-9. [PMID: 12529348]

29. Coogan PF, Rosenberg L, Louik C, Zauber AG, Stolley PD, Strom BL, et al. NSAIDs and risk of colorectal cancer according to presence or absence of family history of the disease. Cancer Causes Control 2000;11:249-55. [PMID: 10782659]

30. Collet JP, Sharpe C, Belzile E, Boivin JF, Hanley J, Abenhaim L. Colorectal cancer prevention by non-steroidal anti-inflammatory drugs: effects of dosage and timing. Br J Cancer 1999;81:62-8. [PMID: 10487613]

31. Peleg II, Lubin MF, Cotsonis GA, Clark WS, Wilcox CM. Long-term use of nonsteroidal antiinflammatory drugs and other chemopreventors and risk of subsequent colorectal neoplasia. Dig Dis Sci. 1996;41:1319-26. [PMID: 8689906]

32. Sørensen HT, Friis S, Nørgärd B, Mellemkjaer L, Blot WJ, McLaughlin JK, et al. Risk of cancer in a large cohort of nonaspirin NSAID users: a population-based study. Br J Cancer 2003;88:1687-92. [PMID: 12771981]

33. Smalley W, Ray WA, Daugherty J, Griffin MR. Use of nonsteroidal antiinflammatory drugs and incidence of colorectal cancer: a population-based study. Arch Intern Med 1999;159:161-6. [PMID: 9927099]

34. Chan AT, Giovannucci EL, Meyerhardt JA, Schernhammer ES, Curhan GC, Fuchs CS. Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. JAMA 2005;294:914-23. [PMID: 16118381]

35. Bigler J, Whitton J, Lampe JW, Fosdick L, Bostick RM, Potter JD. CYP2C9 and UGT1A6 genotypes modulate the protective effect of aspirin on colon adenoma risk. Cancer Res 2001;61:3566-9. [PMID: 11325819]

36. Logan RF, Little J, Hawtin PG, Hardcastle JD. Effect of aspirin and nonsteroidal anti-inflammatory drugs on colorectal adenomas: case-control study of subjects participating in the Nottingham faecal occult blood screening programme. BMJ 1993;307:285-9. [PMID: 8374373]

37. Boyapati SM, Bostick RM, McGlynn KA, Fina MF, Roufail WM, Geisinger KR, et al. Calcium, vitamin D, and risk for colorectal adenoma: dependency on vitamin D receptor BsmI polymorphism and nonsteroidal anti-inflammatory drug use? Cancer Epidemiol Biomarkers Prev 2003;12:631-7. [PMID: 12869402]

38. García Rodríguez LA, Huerta-Alvarez C. Reduced incidence of colorectal adenoma among long-term users of nonsteroidal antiinflammatory drugs: a pooled analysis of published studies and a new population-based study. Epidemiology 2000;11:376-81. [PMID: 10874542]

39. Breuer-Katschinski B, Nemes K, Rump B, Leiendecker B, Marr A, Breuer N, et al. Long-term use of nonsteroidal antiinflammatory drugs and the risk of colorectal adenomas. The Colorectal Adenoma Study Group. Digestion 2000; 61:129-34. [PMID: 10705177]

40. Sandler RS, Galanko JC, Murray SC, Helm JF, Woosley JT. Aspirin and nonsteroidal anti-inflammatory agents and risk for colorectal adenomas. Gastroenterology 1998;114:441-7. [PMID: 9496933]

41. Martínez ME, McPherson RS, Levin B, Annegers JF. Aspirin and other nonsteroidal anti-inflammatory drugs and risk of colorectal adenomatous polyps among endoscoped individuals. Cancer Epidemiol Biomarkers Prev 1995;4:703-7. [PMID: 8672985]

42. Lieberman DA, Prindiville S, Weiss DG, Willett W. Risk factors for advanced colonic neoplasia and hyperplastic polyps in asymptomatic individuals. JAMA 2003;290:2959-67. [PMID: 14665657]

43. Martin C, Connelly A, Keku TO, Mountcastle SB, Galanko J, Woosley JT, et al. Nonsteroidal anti-inflammatory drugs, apoptosis, and colorectal adenomas. Gastroenterology 2002;123:1770-7. [PMID: 12454832]

44. Tangrea JA, Albert PS, Lanza E, Woodson K, Corle D, Hasson M, et al. Non-steroidal anti-inflammatory drug use is associated with reduction in recurrence of advanced and non-advanced colorectal adenomas (United States). Cancer Causes Control 2003;14:403-11. [PMID: 12946034]

45. Ladenheim J, Garcia G, Titzer D, Herzenberg H, Lavori P, Edson R, et al. Effect of sulindac on sporadic colonic polyps. Gastroenterology 1995;108:1083-7. [PMID: 7698575]

46. Giovannucci E, Egan KM, Hunter DJ, Stampfer MJ, Colditz GA, Willett WC, et al. Aspirin and the risk of colorectal cancer in women. N Engl J Med 1995;333:609-14. [PMID: 7637720]

47. Chan AT, Giovannucci EL, Schernhammer ES, Colditz GA, Hunter DJ, Willett WC, et al. A prospective study of aspirin use and the risk for colorectal adenoma. Ann Intern Med 2004;140:157-66. [PMID: 14757613]

48. Dubé C, Rostom A, Lewin G, Tsertsvadze A, Barrowman N, Code C, et al. The use of aspirin for the primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med 2007:146;365-75.

49. Friedman GD, Coates AO, Potter JD, Slattery ML. Drugs and colon cancer. Pharmacoepidemiol Drug Saf 1998;7:99-106. [PMID: 15073733]

50. Morimoto LM, Newcomb PA, Ulrich CM, Bostick RM, Lais CJ, Potter JD. Risk factors for hyperplastic and adenomatous polyps: evidence for malignant potential? Cancer Epidemiol Biomarkers Prev 2002;11:1012-8. [PMID: 12376501]

51. Hauret KG, Bostick RM, Matthews CE, Hussey JR, Fina MF, Geisinger KR, et al. Physical activity and reduced risk of incident sporadic colorectal adenomas: observational support for mechanisms involving energy balance and inflammation modulation. Am J Epidemiol 2004;159:983-92. [PMID: 15128611]

52. 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. [PMID: 15475342]

53. Garner S, Fidan D, Frankish R, Judd M, Shea B, Towheed T, et al. Celecoxib for rheumatoid arthritis. Cochrane Database Syst Rev 2002: CD003831. [PMID: 12519610]

54. Garner SE, Fidan DD, Frankish RR, Judd MG, Towheed TE, Wells G, et al. Rofecoxib for rheumatoid arthritis. Cochrane Database Syst Rev 2005: CD003685. [PMID: 15674912]

55. Tramèr MR, Moore RA, Reynolds DJ, McQuay HJ. Quantitative estimation of rare adverse events which follow a biological progression: a new model applied to chronic NSAID use. Pain 2000;85:169-82. [PMID: 10692616]

56. 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;332:1302-8. [PMID: 16740558]

57. Gomez Cerezo J, Lubomirov Hristov R, Carcas Sansuán AJ, Vázquez Rodríguez JJ. Outcome trials of COX-2 selective inhibitors: global safety evaluation does not promise benefits. Eur J Clin Pharmacol 2003;59:169-75. [PMID: 12698301]

58. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 2001;286:954-9. [PMID: 11509060]

59. Jüni P, Nartey L, Reichenbach S, Sterchi R, Dieppe PA, Egger M. Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet 2004;364: 2021-9. [PMID: 15582059]

60. Edwards JE, McQuay HJ, Moore RA. Efficacy and safety of valdecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomised controlled trials. Pain 2004;111:286-96. [PMID: 15363872]

61. Garner SE, Fidan DD, Frankish R, Maxwell L. Rofecoxib for osteoarthritis.Cochrane Database Syst Rev 2005:CD005115. [PMID: 15654705]

62. Zhang J, Ding EL, Song Y. Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomized trials. JAMA 2006; 296:1619-32. [PMID: 16968832]

63. 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;29:804-12. [PMID: 11950025]

64. Ofman JJ, Maclean CH, Straus WL, Morton SC, Berger ML, Roth EA, et al. Meta-analysis of dyspepsia and nonsteroidal antiinflammatory drugs. Arthritis Rheum 2003;49:508-18. [PMID: 12910557]

65. Huang JQ, Sridhar S, Hunt RH. Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis. Lancet 2002;359:14-22. [PMID: 11809181]

66. Ashcroft DM, Chapman SR, Clark WK, Millson DS. Upper gastroduodenal ulceration in arthritis patients treated with celecoxib. Ann Pharmacother 2001;35:829-34. [PMID: 11485128]

67. 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. [PMID: 12242171]

68. Rigau J, Piqué JM, Rubio E, Planas R, Tarrech JM, Bordas JM. Effects of long-term sulindac therapy on colonic polyposis. Ann Intern Med 1991;115: 952-4. [PMID: 1659272]

69. Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 1998;93:705-16. [PMID: 9630216]

70. Goldstein JL, Eisen GM, Agrawal N, Stenson WF, Kent JD, Verburg KM. Reduced incidence of upper gastrointestinal ulcer complications with the COX-2 selective inhibitor, valdecoxib. Aliment Pharmacol Ther 2004;20:527-38. [PMID: 15339324]

71. Eisen GM, Goldstein JL, Hanna DB, Rublee DA. Meta-analysis: upper gastrointestinal tolerability of valdecoxib, a cyclooxygenase-2-specific inhibitor, compared with nonspecific nonsteroidal anti-inflammatory drugs among patients with osteoarthritis and rheumatoid arthritis. Aliment Pharmacol Ther 2005;21: 591-8. [PMID: 15740543]

72. Schoenfeld P. Gastrointestinal safety profile of meloxicam: a meta-analysis and systematic review of randomized controlled trials. Am J Med 1999;107:48S-54S. [PMID: 10628593]

73. Silverstein FE, Graham DY, Senior JR, Davies HW, Struthers BJ, Bittman 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;123:241-9. [PMID: 7611589]

74. 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. Celecoxib Long-term Arthritis Safety Study. JAMA 2000;284:1247-55. [PMID: 10979111]

75. Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000; 343:1520-8, 2 p following 1528. [PMID: 11087881]

76. Schnitzer TJ, Burmester GR, Mysler E, Hochberg MC, Doherty M, Ehrsam E, et al. 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: 665-74. [PMID: 15325831]

77. Singh G, Fort JG, Goldstein JL, Levy RA, Hanrahan PS, Bello AE, et al. Celecoxib versus naproxen and diclofenac in osteoarthritis patients: SUCCESS-I Study. Am J Med 2006; 19:255-66. [PMID: 16490472]

78. Topol EJ. Failing the public health—rofecoxib, Merck, and the FDA. N Engl J Med 2004;351:1707-9. [PMID: 15470193]

79. Topol EJ. Arthritis medicines and cardiovascular events—"house of coxibs" [Editorial]. JAMA 2005;293:366-8. [PMID: 15623849]

80. Health Canada. Advisory Committee Briefing Document. Celecoxib Valdecoxib Cardiovascular Safety. Accessed at www.hc-sc.gc.ca/dhp_mps/alt_formats/hpfb-dgpsa/pdf/prodpharma/sap_report_gcs_rappurt_cox2_e.pdf on 20 January 2005.

81. U.S. Food and Drug Administration. Arthritis & Drug Safety and Risk Management Advisory Committee Briefing Package. Accessed at www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4090b1-01.htm on 20 January 2005.

82. 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. [PMID: 15947398]

83. Watson DJ, Rhodes T, Cai B, Guess HA. Lower risk of thromboembolic cardiovascular events with naproxen among patients with rheumatoid arthritis. Arch Intern Med 2002;162:1105-10. [PMID: 12020179]

84. Ray WA, Stein CM, Hall K, Daugherty JR, Griffin MR. Non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease: an observational cohort study. Lancet 2002;359:118-23. [PMID: 11809254]

85. Lynch PM. Is the demonstration of adenoma reduction with rofecoxib a pyrrhic victory? [Editorial]. Gastroenterology 2006;131:2003-5. [PMID: 17188962]

86. Psaty BM, Potter JD. Risks and benefits of celecoxib to prevent recurrent adenomas [Editorial]. N Engl J Med 2006;355:950-2. [PMID: 16943408]

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The investigators thank Mary White, Sc.D., Chief Epidemiology and Applied Research Branch (CDC); Patrik Johansson, M.D., Medical Officer (AHRQ); Therese Miller, Dr.P.H., Task Order Officer (AHRQ); Janelle Guirguis-Blake, M.D., USPSTF Program Director; and Elizabeth A. Edgerton, M.D., M.P.H., Director of Clinical Prevention. They also thank members of the USPSTF who served as leads for the project: Ned Calonge, M.D., M.P.H.; Michael LeFevre, M.D., M.S.P.H.; Carol Loveland-Cherry, Ph.D., R.N.; and Al Siu, M.D., M.S.P.H. They thank Nav Saloojee, M.D., for helping in the selection of relevant reports; Tiffany Richards for assisting with the evidence tables; Raymond Daniel for retrieving the full reports; Chantelle Garritty for helping to coordinate the process; and Isabella Steffensen and Christine Murray for dedicating many long hours to editing the report and its appendix tables.

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Author Affiliation

a. Drs. Dubé and Rostom: Division of Gastroenterology, University of Calgary Medical Clinic, Calgary, Alberta, Canada.
b. Drs. Lewin, Tsertsvadze, Barrowman, Sampson, and Moher: Chalmers Research Group, CHEO Research Institute, Ottawa, Ontario Canada.
c. Dr. Code: Division of Internal Medicine, The Ottawa Hospital—Civic Site, Ottawa, Ontario Canada.

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Source: Rostom A, Dubé C, Lewin G, Tsertsvadze A, Barrowman N, Code C, Sampson M, Moher D. Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for primary prevention of colorectal cancer: Systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2007;146:376-89.

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Current as of March 2007

Internet Citation:

Rostom A, Dubé C, Lewin G, Tsertsvadze A, Barrowman N, Code C, Sampson M, Moher D. Nonsteroidal Anti-inflammatory Drugs and Cyclooxygenase-2 Inhibitors for Primary Prevention of Colorectal Cancer: Systematic Review for the U.S. Preventive Services Task Force. Originally published in Ann Intern Med 2007;146:376-89. March 2007. http://www.uspreventiveservicestaskforce.org/uspstf07/aspcolo/nsaidsrev.htm


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