title: Statin use and colorectal adenoma risk: results from the adenoma prevention with celecoxib trial.
abstract: Statins are widely prescribed for cardiovascular disease prevention and also commonly used in patients at high risk for colorectal cancer. We report the results of a planned secondary analysis of the relationship between statin use and colorectal adenoma risk in a large chemoprevention trial. The Adenoma Prevention with Celecoxib (APC) trial randomized 2,035 adenoma patients to receive placebo (679 patients), 200 mg celecoxib twice daily (bid; 685 patients), or 400 mg celecoxib bid (671 patients). The study collected complete medical history and medication use data and performed colonoscopic surveillance to 5 years after study enrollment. The effects of statin use on newly detected adenomas and cardiovascular adverse events were analyzed as time-dependent variables by multivariable Cox regression. Statins were used by 36% (n = 730) of APC trial participants. When adjusted for covariates including cardioprotective aspirin use, age, and sex, participants on the placebo arm who used statins at any time had no benefit over 5 years compared with never users (risk ratio, 1.24; 95% confidence interval, 0.99-1.56; P = 0.065). Statin use for >3 years increased adenoma risk over 5 years (risk ratio, 1.39; 95% confidence interval, 1.04-1.86; P = 0.024). For all comparisons of patients treated with celecoxib, adenoma detection rates for statin users and nonusers were equivalent. Consistent with their use in patients at high risk, cardiovascular serious adverse events were more common among statin users. For patients at high risk of colorectal cancer, statins do not protect against colorectal neoplasms and may even increase the risk of developing colorectal adenomas.
authors.affiliation: Brigham and Women's Hospital, Boston, MA 02115, USA. mbertagnolli@partners.org
authors.forename: Monica M
authors.initials: MM
authors.lastname: Bertagnolli
authors.forename: Meier
authors.initials: M
authors.lastname: Hsu
authors.forename: Ernest T
authors.initials: ET
authors.lastname: Hawk
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Eagle
authors.forename: Ann G
authors.initials: AG
authors.lastname: Zauber
mesh_terms: D000236:Adenoma / Q000517:prevention & control*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D000068579:Celecoxib; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000627:therapeutic use*; D016037:Single-Blind Method; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib
references.citation: Cancer Res. 2006 Apr 15;66(8):4542-6
references.pmid: 16618783
references.citation: Gastroenterology. 2007 Aug;133(2):393-402
references.pmid: 17681160
references.citation: Cancer Prev Res (Phila). 2009 Apr;2(4):310-21
references.pmid: 19336730
references.citation: J Clin Oncol. 2007 Aug 10;25(23):3462-8
references.pmid: 17687150
references.citation: Lancet. 2002 Nov 23;360(9346):1623-30
references.pmid: 12457784
references.citation: Int J Cancer. 2010 Jan 1;126(1):279-84
references.pmid: 19739258
references.citation: Am J Ther. 2010 Jul-Aug;17(4):e100-4
references.pmid: 19451806
references.citation: Lancet. 1991 Jun 22;337(8756):1529-31
references.pmid: 1675380
references.citation: N Engl J Med. 2008 Sep 25;359(13):1343-56
references.pmid: 18765433
references.citation: Digestion. 2009;79(1):17-22
references.pmid: 19246916
references.citation: Cancer Res. 2006 Jul 15;66(14):7370-7
references.pmid: 16849589
references.citation: Curr Atheroscler Rep. 2009 Mar;11(2):100-4
references.pmid: 19228482
references.citation: Stat Med. 1998 Oct 15;17(19):2265-81
references.pmid: 9802183
references.citation: Am J Med Sci. 2009 Nov;338(5):378-81
references.pmid: 19794305
references.citation: Circulation. 2007 Jan 2;115(1):27-33
references.pmid: 17179016
references.citation: J Natl Cancer Inst. 2006 Jan 4;98(1):69-72
references.pmid: 16391373
references.citation: N Engl J Med. 2005 May 26;352(21):2184-92
references.pmid: 15917383
references.citation: Nat Rev Cancer. 2005 Dec;5(12):930-42
references.pmid: 16341084
references.citation: N Engl J Med. 2006 Aug 31;355(9):873-84
references.pmid: 16943400
references.citation: Cancer Epidemiol Biomarkers Prev. 2005 Apr;14(4):1026-7
references.pmid: 15824186
references.citation: Pharmacoepidemiol Drug Saf. 2008 Jan;17(1):27-36
references.pmid: 17944002
references.citation: Int J Cancer. 2007 Sep 15;121(6):1325-30
references.pmid: 17487832
references.citation: J Natl Cancer Inst. 2007 Jan 3;99(1):32-40
references.pmid: 17202111
references.citation: N Engl J Med. 2005 Mar 17;352(11):1071-80
references.pmid: 15713944