Impact of urate level on cardiovascular risk in allopurinol-treated patients: A nested case-control study

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Background: Gout gives rise to increased risk of adverse cardiovascular outcomes. Gout attacks can be effectively prevented with urate-lowering drugs such as allopurinol, and allopurinol potentially reduces cardiovascular risk. What target level of urate is required to reduce cardiovascular risk is not known. Objectives: The aim of this study was 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 (antiplatelet trialist's collaboration composite endpoint) and sampled four controls to each case from the same population using risk-set sampling. 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 inpatient and outpatient contacts. Results: No association between treatment-to-target urate level and cardiovascular events was 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. However, the results are limited by the low doses of allopurinol used. Possible explanations include that higher allopurinol doses 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.
Original languageEnglish
Article number615
JournalPharmacoepidemiology and Drug Safety
Issue numberS1
Pages (from-to)351-352
Number of pages2
Publication statusPublished - 2015
Event31st International Conference on Pharmacoepidemiology and Therapeutic Risk Management - Boston, United States
Duration: 22. Aug 201526. Aug 2015


Conference31st International Conference on Pharmacoepidemiology and Therapeutic Risk Management
CountryUnited States

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