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

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Abstract

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 further potentially reduces the cardiovascular risk. Whether treatment to a target level of uric acid is required to reduce cardiovascular risk is not known. Objectives: We sought 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 all 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 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 or in- and outpatient contacts. Results: No association of treatment-to-target urate level below 0.36 mmol/l and cardiovascular events were found. Adjusted odds ratio for cardiovascular event between cases and controls was 1.01 (95% confidence interval 0.80 - 1.29). No significant effect was seen in any subgroup when stratifying 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/d). Conclusions: In our study, we were unable to demonstrate any effect of the achieved urate level in patients treated with allopurinol on cardiovascular events. However, the results are hampered by the low doses of allopurinol used. Possible explanations include that higher allopurinol doses are required to achieve cardiovascular risk reduction or that the putative effect of allopurinol on cardiovascular risk is not mediated through urate levels. It remains to be seen whether allopurinol has a dose-response relationship with cardiovascular events at higher doses.
Original languageEnglish
Article numberAB0921
JournalAnnals of the Rheumatic Diseases
Volume74
Issue numberS2
Pages (from-to)1208
Number of pages1
ISSN0003-4967
DOIs
Publication statusPublished - 2015
EventEULAR 2015: Annual European Congress of Rheumatology - Fiera Roma, Rom, Italy
Duration: 10. Jun 201513. Jun 2015

Conference

ConferenceEULAR 2015
LocationFiera Roma
CountryItaly
CityRom
Period10/06/201513/06/2015

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