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

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Resumé

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.

OriginalsprogEngelsk
Artikelnummere0146172
TidsskriftP L o S One
Vol/bind11
Udgave nummer1
Sider (fra-til)1-13
ISSN1932-6203
DOI
StatusUdgivet - 2016

Fingeraftryk

allopurinol
Allopurinol
case-control studies
Uric Acid
Case-Control Studies
gout
dosage
odds ratio
Odds Ratio
risk reduction
renal function
Denmark
Risk Reduction Behavior
dose response
Prescriptions
Inpatients
confidence interval
Outpatients

Citer dette

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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.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.",
author = "{S{\o}ltoft Larsen}, Kasper and Anton Potteg{\aa}rd and Lindegaard, {Hanne M} and Jesper Hallas",
year = "2016",
doi = "10.1371/journal.pone.0146172",
language = "English",
volume = "11",
pages = "1--13",
journal = "P L o S One",
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Impact of Urate Level on Cardiovascular Risk in Allopurinol Treated Patients. A Nested Case-Control Study. / Søltoft Larsen, Kasper; Pottegård, Anton; Lindegaard, Hanne M; Hallas, Jesper.

I: P L o S One, Bind 11, Nr. 1, e0146172, 2016, s. 1-13.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Impact of Urate Level on Cardiovascular Risk in Allopurinol Treated Patients. A Nested Case-Control Study

AU - Søltoft Larsen, Kasper

AU - Pottegård, Anton

AU - Lindegaard, Hanne M

AU - Hallas, Jesper

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0146172

DO - 10.1371/journal.pone.0146172

M3 - Journal article

VL - 11

SP - 1

EP - 13

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 1

M1 - e0146172

ER -