title: Impact of Urate Level on Cardiovascular Risk in Allopurinol Treated Patients. A Nested Case-Control Study.
abstract: BACKGROUND
  Gout gives rise to increased risk of cardiovascular events. Gout attacks can be effectively prevented with urate lowering drugs, and allopurinol potentially reduces cardiovascular risk. What target level of urate is required to reduce cardiovascular risk is not known.
  
  
  OBJECTIVE
  To investigate the effect of achieving target plasma urate with allopurinol on cardiovascular outcomes in a case-control study nested within long-term users of allopurinol.
  
  
  METHODS
  We identified long-term users of allopurinol in Funen County, Denmark. Among these, we identified all cases of cardiovascular events and sampled 4 controls to each case from the same population. The cases and controls were compared with respect to whether they reached a urate target below 0.36 mmol/l on allopurinol. The derived odds ratios were controlled for potential confounders available from data on prescriptions, laboratory values and in- and outpatient contacts.
  
  
  RESULTS
  No association between treatment-to-target urate level and cardiovascular events were found (adjusted odds ratio of 1.01, 95% confidence interval 0.79-1.28). No significant effect was seen in any subgroup defined by age, gender, renal function, allopurinol dose or the achieved urate level. Overall, the doses of allopurinol used in this study were low (mean ≈ 140 mg/day).
  
  
  CONCLUSIONS
  We were unable to demonstrate a link between achieved urate level in patients treated with allopurinol and risk of cardiovascular events. Possible explanations include that allopurinol doses higher than those used in this study are required to achieve cardiovascular risk reduction or that the cardiovascular effect of allopurinol is not mediated through low urate levels. It remains to be seen whether allopurinol has a dose-response relationship with cardiovascular events at higher doses.
authors.affiliation: Clinical Pharmacology, Department of Public Health, University of Southern Denmark, JB Winsloewvej 19.2, DK-5000, Odense C, Denmark.|Department of Rheumatology, Odense University Hospital, Sdr. Boulevard 29, DK-5000, Odense C, Denmark.
authors.forename: Kasper
authors.initials: K
authors.lastname: Søltoft Larsen
authors.affiliation: Clinical Pharmacology, Department of Public Health, University of Southern Denmark, JB Winsloewvej 19.2, DK-5000, Odense C, Denmark.
authors.forename: Anton
authors.initials: A
authors.lastname: Pottegård
authors.affiliation: Department of Rheumatology, Odense University Hospital, Sdr. Boulevard 29, DK-5000, Odense C, Denmark.
authors.forename: Hanne M
authors.initials: HM
authors.lastname: Lindegaard
authors.affiliation: Clinical Pharmacology, Department of Public Health, University of Southern Denmark, JB Winsloewvej 19.2, DK-5000, Odense C, Denmark.|Department of Clinical Chemistry & Pharmacology, Odense University Hospital, JB Winsloewvej 19.2, DK-5000, Odense C, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Hallas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000097:blood*; D016022:Case-Control Studies; D003718:Denmark; D004305:Dose-Response Relationship, Drug; D005260:Female; D006073:Gout / Q000517:prevention & control; D006074:Gout Suppressants / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D015203:Reproducibility of Results; D012307:Risk Factors; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood*
chemical_list: D006074:Gout Suppressants; D014527:Uric Acid; D000493:Allopurinol