title: Low-dose aspirin in the primary prevention of rheumatoid arthritis: the Women's Health Study.
abstract: OBJECTIVE
  Low-dose aspirin may reduce the risk of developing rheumatoid arthritis (RA) through its effect on cyclooxygenase activity and its antioxidant pathways. Previous randomized trial data have demonstrated a beneficial effect of low-dose aspirin in reducing other inflammatory diseases, such as asthma and colorectal adenomas, but no trial has evaluated the role of aspirin in RA prevention.
  
  
  METHODS
  The Women's Health Study is a randomized, double-blind, placebo-controlled trial conducted between 1992 and 2004 designed to evaluate the risks and benefits of low-dose aspirin (100 mg every other day) and vitamin E in the primary prevention of cardiovascular disease and cancer among 39,876 female health care professionals age > or =45 years throughout the US. After excluding women with RA at baseline, 39,144 women were evaluated for the present study. A definite diagnosis of RA was assessed during followup by self-report and confirmed using a connective tissue disease screening questionnaire, followed by a medical record review by a rheumatologist for American College of Rheumatology criteria.
  
  
  RESULTS
  During an average followup of 10 years, 106 women developed definite RA (48 women in the aspirin group and 58 in the placebo group). There was a nonsignificant risk for RA (relative risk [RR] 0.83, 95% confidence interval [95% CI] 0.56-1.21; P = 0.33) associated with aspirin. There were 64 seropositive RA cases (60%) and 42 seronegative RA cases (40%). Aspirin also had no significant effect on either seropositive RA (RR 1.0, 95% CI 0.61-1.63) or seronegative RA (RR 0.62, 95% CI 0.33-1.15).
  
  
  CONCLUSIONS
  One hundred milligrams of aspirin taken every other day was not associated with a significant reduction in the risk of developing RA among women in a randomized, double-blind, placebo-controlled trial.
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. nshadick@partners.org
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Shadick
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Karlson
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Cook
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Maher
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.forename: I-Min
authors.initials: IM
authors.lastname: Lee
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000517:prevention & control*; D001241:Aspirin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D011322:Primary Prevention; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012306:Risk
chemical_list: D000893:Anti-Inflammatory Agents; D001241:Aspirin
references.citation: Arthritis Rheum. 1998 Aug;41(8):1481-8
references.pmid: 9704648
references.citation: N Engl J Med. 1989 Jul 20;321(3):183-5
references.pmid: 2747748
references.citation: MMWR Morb Mortal Wkly Rep. 1997 Jun 6;46(22):498-502
references.pmid: 9194401
references.citation: J Natl Cancer Inst. 2002 Feb 20;94(4):252-66
references.pmid: 11854387
references.citation: Epidemiology. 2000 Jul;11(4):371-4
references.pmid: 10874540
references.citation: J Immunol. 2002 Feb 1;168(3):1428-34
references.pmid: 11801685
references.citation: Arthritis Rheum. 1999 Mar;42(3):415-20
references.pmid: 10088762
references.citation: Circulation. 2000 Mar 14;101(10):1206-18
references.pmid: 10715270
references.citation: Arthritis Rheum. 2008 Nov 15;59(11):1589-95
references.pmid: 18975365
references.citation: Am J Med. 2002 Apr 15;112(6):465-71
references.pmid: 11959057
references.citation: JAMA. 2004 May 26;291(20):2433-40
references.pmid: 15161893
references.citation: Am J Epidemiol. 1980 Jan;111(1):87-98
references.pmid: 7352462
references.citation: J Rheumatol. 2000 Dec;27(12):2743-6
references.pmid: 11128658
references.citation: Endocrinology. 1996 Dec;137(12):5739-42
references.pmid: 8940410
references.citation: Arthritis Rheum. 2003 Oct;48(10):2741-9
references.pmid: 14558078
references.citation: JAMA. 2005 Jul 6;294(1):47-55
references.pmid: 15998890
references.citation: Science. 1994 Aug 12;265(5174):956-9
references.pmid: 8052854
references.citation: Thorax. 2008 Jun;63(6):514-8
references.pmid: 18339679
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Apr;13(4):649-53
references.pmid: 15066932
references.citation: N Engl J Med. 2005 Mar 31;352(13):1293-304
references.pmid: 15753114
references.citation: Lupus. 2005;14(10):832-6
references.pmid: 16304727
references.citation: Arthritis Rheum. 1988 Mar;31(3):315-24
references.pmid: 3358796
references.citation: JAMA. 2006 Jul 26;296(4):391; author reply 391-2
references.pmid: 16868289
references.citation: Arthritis Rheum. 2003 Nov;48(11):3055-60
references.pmid: 14613266
references.citation: Br J Cancer. 2004 Aug 2;91(3):525-9
references.pmid: 15226764
references.citation: Arthritis Rheum. 1991 Dec;34(12):1502-7
references.pmid: 1747134
references.citation: Dis Colon Rectum. 2004 May;47(5):665-73
references.pmid: 15054679
references.citation: Ann Epidemiol. 1995 Jul;5(4):297-302
references.pmid: 8520712