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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.

Objectives

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).

Conclusion

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.

SUBMITTER: Soltoft Larsen K 

PROVIDER: S-EPMC4709004 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Impact of Urate Level on Cardiovascular Risk in Allopurinol Treated Patients. A Nested Case-Control Study.

Søltoft Larsen Kasper K   Pottegård Anton A   Lindegaard Hanne M HM   Hallas Jesper J  

PloS one 20160111 1


<h4>Background</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>We ide  ...[more]

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