title: Cardiovascular risk in rheumatoid arthritis: comparing TNF-α blockade with nonbiologic DMARDs.
abstract: BACKGROUND
  Elevated tumor necrosis factor (TNF)-α likely contributes to the excess cardiovascular risk observed in rheumatoid arthritis. We compared the cardiovascular risk in rheumatoid arthritis patients starting a TNF-α blocking agent versus a nonbiologic disease-modifying antirheumatic drug (nbDMARD).
  
  
  METHODS
  Subjects with rheumatoid arthritis participating in several different US insurance programs between 1998 and 2007 who received methotrexate were eligible. Those who added a TNF-α blocking agent were compared with subjects who added a nbDMARD in Cox regression models stratified by propensity score decile and adjusted for oral glucocorticoid dosage. We examined the composite cardiovascular end point of myocardial infarction, stroke, or coronary re-vascularization after 6 months.
  
  
  RESULTS
  We compared 8656 new users of a nbDMARD with 11,587 new users of a TNF-α blocking agent with similar baseline covariates. Incidence rates per 100 person-years for the composite cardiovascular end point were 3.05 (95% confidence interval [CI], 2.54-3.65) for nbDMARDs and 2.52 (95% CI, 2.12-2.98) for TNF-α blocking agents. The hazard ratio (HR) for the TNF-α blocking agent compared with nbDMARD carrying the first exposure forward was 0.80 (95%, CI 0.62-1.04), while the HR for the as-treated analysis was 0.71 (95% CI, 0.52-0.97). The potential cardiovascular benefit of TNF-α blocking agents was strongest among individuals ≥65 years of age (HR 0.52; 95% CI, 0.34 -0.77; P for interaction = 0.075).
  
  
  CONCLUSIONS
  Among subjects with rheumatoid arthritis, TNF-α blocking agents may be associated with a reduced risk of cardiovascular events compared with an nbDMARD. Randomized controlled clinical trials should be considered to test this hypothesis.
authors.affiliation: Brigham and Women's Hospital, Boston, MA 02115, USA. dhsolomon@partners.org
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Solomon
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Saag
authors.forename: Joyce
authors.initials: J
authors.lastname: Lii
authors.forename: Lang
authors.initials: L
authors.lastname: Chen
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Harrold
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Herrinton
authors.forename: David J
authors.initials: DJ
authors.lastname: Graham
authors.forename: Mary K
authors.initials: MK
authors.lastname: Kowal
authors.forename: Bindee
authors.initials: B
authors.lastname: Kuriya
authors.forename: Liyan
authors.initials: L
authors.lastname: Liu
authors.forename: Marie R
authors.initials: MR
authors.lastname: Griffin
authors.forename: James D
authors.initials: JD
authors.lastname: Lewis
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Rassen
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000150:complications / Q000517:prevention & control*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D009204:Myocardial Revascularization; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012306:Risk; D020521:Stroke / Q000517:prevention & control; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate
keywords: Cardiovascular disease; Rheumatoid arthritis; TNF-α blocking agents