title: Effects of xanthine oxidase inhibitors on cardiovascular disease in patients with gout: a cohort study.
abstract: BACKGROUND
  Hyperuricemia and gout are associated with an increased risk of cardiovascular disease (CVD). It is unknown whether treating hyperuricemia with xanthine oxidase inhibitors (XOIs), including allopurinol and febuxostat, modifies cardiovascular risks.
  
  
  METHODS
  We used US insurance claims data to conduct a cohort study among gout patients, comparing XOI initiators with non-users with hyperuricemia defined as serum uric acid level ≥6.8 mg/dL. We calculated incidence rates of a composite nonfatal cardiovascular outcome that included myocardial infarction, coronary revascularization, stroke, and heart failure. Propensity score (PS)-matched Cox proportional hazards regression compared the risk of composite cardiovascular endpoint in XOI initiators vs those with untreated hyperuricemia, controlling for baseline confounders. In a subgroup of patients with uric acid levels available, PS-matched Cox regression further adjusted for baseline uric acid levels.
  
  
  RESULTS
  There were 24,108 PS-matched pairs with a mean age of 51 years and 88% male. The incidence rate per 1000 person-years for composite CVD was 24.1 (95% confidence interval [CI] 22.6-26.0) in XOI initiators and 21.4 (95% CI, 19.8-23.2) in the untreated hyperuricemia group. The PS-matched hazard ratio for composite CVD was 1.16 (95% CI, 0.99-1.34) in XOI initiators vs those with untreated hyperuricemia. In subgroup analyses, the PS-matched hazard ratio for composite CVD adjusted for serum uric acid levels was 1.10 (95% CI, 0.74-1.64) among XOI initiators.
  
  
  CONCLUSIONS
  Among patients with gout, initiation of XOI was not associated with an increased or decreased cardiovascular risk compared with those with untreated hyperuricemia. Subgroup analyses adjusting for baseline uric acid levels also showed no association between XOI and cardiovascular risk.
authors: Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, Mass; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Mass; Department of Epidemiology, Harvard School of Public Health, Boston, Mass. Electronic address: skim62@partners.org.
authors: Seoyoung C
authors: SC
authors: Kim
authors: Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, Mass; Department of Epidemiology, Harvard School of Public Health, Boston, Mass.
authors: Sebastian
authors: S
authors: Schneeweiss
authors: Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, Mass.
authors: Niteesh
authors: N
authors: Choudhry
authors: Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, Mass.
authors: Jun
authors: J
authors: Liu
authors: Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, Mass.
authors: Robert J
authors: RJ
authors: Glynn
authors: Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, Mass; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Mass.
authors: Daniel H
authors: DH
authors: Solomon
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D006073:Gout / Q000188:drug therapy*; D006074:Gout Suppressants / Q000009:adverse effects / Q000627:therapeutic use*; D006331:Heart Diseases / Q000209:etiology*; D006801:Humans; D033461:Hyperuricemia / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
chemical_list: D006074:Gout Suppressants; D014969:Xanthine Oxidase
keywords: Allopurinol; Cardiovascular disease; Febuxostat; Gout; Heart failure; Myocardial infarction; Stroke; Xanthine oxidase inhibitor