title: Effect of Allopurinol on Cardiovascular Outcomes in Hyperuricemic Patients: A Cohort Study.
abstract: BACKGROUND
  Hyperuricemia and gout have been associated with increased cardiovascular risk. Allopurinol is an effective urate-lowering drug. Whether lowering of urate by allopurinol improves the cardiovascular risk in hyperuricemic patients remains to be established.
  
  
  OBJECTIVE
  Our objective was to investigate the effect of allopurinol on cardiovascular outcomes in hyperuricemic patients in an observational setting.
  
  
  METHODS
  We had access to a study population consisting of all patients from Funen County, Denmark with high urate levels (≥6 mg/dL) from 1992 to 2010. We linked 4 registries; all blood samples, all in- and outpatient contacts in hospitals, all reimbursed prescriptions and causes of death. We identified all incident allopurinol users and matched them 1:1 to nonusers of urate-lowering therapy, with similar urate levels, by using propensity scores. Hazard ratios were calculated using competing risk regression model, with respect to Antiplatelet Trialists' Collaboration composite outcome (myocardial infarction, stroke, or cardiovascular death) and all-cause mortality.
  
  
  RESULTS
  Among 65,971 patients with hyperuricemia, we found 7127 patients on allopurinol treatment. In the propensity score-matched cohort we found a hazard ratio of 0.89 (95% confidence interval, 0.81-0.97) for the main outcome among allopurinol treated compared with nonusers of allopurinol. The corresponding hazard ratio for all-cause mortality was 0.68 (95% confidence interval, 0.62-0.74).
  
  
  CONCLUSIONS
  Allopurinol treatment is associated with a decreased cardiovascular risk among hyperuricemic patients.
authors.affiliation: Department of Clinical Chemistry & Pharmacology, Odense University Hospital, Odense C, Denmark; Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense C, Denmark; Department of Rheumatology, Odense University Hospital, Odense C, Denmark. Electronic address: kaslarsen@health.sdu.dk.
authors.forename: Kasper Søltoft
authors.initials: KS
authors.lastname: Larsen
authors.affiliation: Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense C, Denmark.
authors.forename: Anton
authors.initials: A
authors.lastname: Pottegård
authors.affiliation: Department of Rheumatology, Odense University Hospital, Odense C, Denmark.
authors.forename: Hanne M
authors.initials: HM
authors.lastname: Lindegaard
authors.affiliation: Department of Clinical Chemistry & Pharmacology, Odense University Hospital, Odense C, Denmark; Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense C, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Hallas
mesh_terms: D000368:Aged; D000493:Allopurinol / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality*; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D033461:Hyperuricemia / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology*; D057216:Propensity Score; D012042:Registries; D020521:Stroke / Q000453:epidemiology*
chemical_list: D006074:Gout Suppressants; D000493:Allopurinol
keywords: Allopurinol; Cardiovascular outcomes; Gout; Hyperuricemia