Impact of allopurinol use on urate concentration and cardiovascular outcome

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Guidelines recommend that the therapeutic goal of urate‐lowering therapy (ULT) is to achieve a urate concentration of ≤6 mg dl−1. • High‐dose allopurinol is associated with reduced cardiovascular events and mortality in heart failure patients. WHAT THIS STU...

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Vydáno v:British journal of clinical pharmacology Ročník 71; číslo 4; s. 600 - 607
Hlavní autoři: Wei, Li, Mackenzie, Isla S., Chen, Yang, Struthers, Allan D., MacDonald, Thomas M.
Médium: Journal Article
Jazyk:angličtina
Vydáno: Oxford, UK Blackwell Publishing Ltd 01.04.2011
Blackwell
Blackwell Science Inc
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ISSN:0306-5251, 1365-2125, 1365-2125
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Abstract WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Guidelines recommend that the therapeutic goal of urate‐lowering therapy (ULT) is to achieve a urate concentration of ≤6 mg dl−1. • High‐dose allopurinol is associated with reduced cardiovascular events and mortality in heart failure patients. WHAT THIS STUDY ADDS • Less than 50% of patients taking allopurinol reached target urate concentration. • Higher doses of allopurinol were associated with better control of urate and lower risks of both cardiovascular events and mortality in all patients on allopurinol treatment. AIMS To characterize patients with urate measurements by urate‐lowering therapy (ULT) use and to study the impact of allopurinol treatment on cardiovascular and mortality outcomes. METHODS A cohort study using a record‐linkage database. The study included 7135 patients aged ≥60 years with urate measurements between 2000 and 2002 followed up until 2007. A Cox regression model was used. The association between urate levels, dispensed allopurinol and cardiovascular hospitalization and mortality was determined. RESULTS Six thousand and forty‐two patients were not taking ULT and 45.9% of those (2774 of 6042) had urate concentrations ≤6 mg dl−1. Among 1035 allopurinol users, 44.7% (45.6% for men and 43.3% for women) reached target urate concentration. There was no significant increased risk of cardiovascular events for allopurinol users when compared with non‐ULT users [adjusted hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.95–1.26] and the non‐ULT group with urate >6 mg dl−1 (adjusted HR 1.07, 95% CI 0.89–1.28). Within the allopurinol use cohort, cardiovascular event rates were 74.0 (95% CI 61.9–86.1) per 1000 person years for the 100 mg group, 69.7 (49.6–89.8) for the 200 mg group and 47.6 (38.4–56.9) for the ≥300 mg group. Compared with low‐dose (100 mg) users, high‐dose (≥300 mg) users had significant reductions in the risk of cardiovascular events (adjusted HR 0.69, 95% CI 0.50–0.94) and mortality (adjusted HR 0.75, 95% CI 0.59–0.94). CONCLUSIONS Less than 50% of patients taking allopurinol reached target urate concentration. Higher doses of allopurinol were associated with better control of urate and lower risks of both cardiovascular events and mortality.
AbstractList To characterize patients with urate measurements by urate-lowering therapy (ULT) use and to study the impact of allopurinol treatment on cardiovascular and mortality outcomes.AIMSTo characterize patients with urate measurements by urate-lowering therapy (ULT) use and to study the impact of allopurinol treatment on cardiovascular and mortality outcomes.A cohort study using a record-linkage database. The study included 7135 patients aged ≥60 years with urate measurements between 2000 and 2002 followed up until 2007. A Cox regression model was used. The association between urate levels, dispensed allopurinol and cardiovascular hospitalization and mortality was determined.METHODSA cohort study using a record-linkage database. The study included 7135 patients aged ≥60 years with urate measurements between 2000 and 2002 followed up until 2007. A Cox regression model was used. The association between urate levels, dispensed allopurinol and cardiovascular hospitalization and mortality was determined.Six thousand and forty-two patients were not taking ULT and 45.9% of those (2774 of 6042) had urate concentrations ≤6 mg dl(-1) . Among 1035 allopurinol users, 44.7% (45.6% for men and 43.3% for women) reached target urate concentration. There was no significant increased risk of cardiovascular events for allopurinol users when compared with non-ULT users [adjusted hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.95-1.26] and the non-ULT group with urate >6 mg dl(-1) (adjusted HR 1.07, 95% CI 0.89-1.28). Within the allopurinol use cohort, cardiovascular event rates were 74.0 (95% CI 61.9-86.1) per 1000 person years for the 100 mg group, 69.7 (49.6-89.8) for the 200 mg group and 47.6 (38.4-56.9) for the ≥300 mg group. Compared with low-dose (100 mg) users, high-dose (≥300 mg) users had significant reductions in the risk of cardiovascular events (adjusted HR 0.69, 95% CI 0.50-0.94) and mortality (adjusted HR 0.75, 95% CI 0.59-0.94).RESULTSSix thousand and forty-two patients were not taking ULT and 45.9% of those (2774 of 6042) had urate concentrations ≤6 mg dl(-1) . Among 1035 allopurinol users, 44.7% (45.6% for men and 43.3% for women) reached target urate concentration. There was no significant increased risk of cardiovascular events for allopurinol users when compared with non-ULT users [adjusted hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.95-1.26] and the non-ULT group with urate >6 mg dl(-1) (adjusted HR 1.07, 95% CI 0.89-1.28). Within the allopurinol use cohort, cardiovascular event rates were 74.0 (95% CI 61.9-86.1) per 1000 person years for the 100 mg group, 69.7 (49.6-89.8) for the 200 mg group and 47.6 (38.4-56.9) for the ≥300 mg group. Compared with low-dose (100 mg) users, high-dose (≥300 mg) users had significant reductions in the risk of cardiovascular events (adjusted HR 0.69, 95% CI 0.50-0.94) and mortality (adjusted HR 0.75, 95% CI 0.59-0.94).Less than 50% of patients taking allopurinol reached target urate concentration. Higher doses of allopurinol were associated with better control of urate and lower risks of both cardiovascular events and mortality.CONCLUSIONSLess than 50% of patients taking allopurinol reached target urate concentration. Higher doses of allopurinol were associated with better control of urate and lower risks of both cardiovascular events and mortality.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Guidelines recommend that the therapeutic goal of urate‐lowering therapy (ULT) is to achieve a urate concentration of ≤6 mg dl−1. • High‐dose allopurinol is associated with reduced cardiovascular events and mortality in heart failure patients. WHAT THIS STUDY ADDS • Less than 50% of patients taking allopurinol reached target urate concentration. • Higher doses of allopurinol were associated with better control of urate and lower risks of both cardiovascular events and mortality in all patients on allopurinol treatment. AIMS To characterize patients with urate measurements by urate‐lowering therapy (ULT) use and to study the impact of allopurinol treatment on cardiovascular and mortality outcomes. METHODS A cohort study using a record‐linkage database. The study included 7135 patients aged ≥60 years with urate measurements between 2000 and 2002 followed up until 2007. A Cox regression model was used. The association between urate levels, dispensed allopurinol and cardiovascular hospitalization and mortality was determined. RESULTS Six thousand and forty‐two patients were not taking ULT and 45.9% of those (2774 of 6042) had urate concentrations ≤6 mg dl−1. Among 1035 allopurinol users, 44.7% (45.6% for men and 43.3% for women) reached target urate concentration. There was no significant increased risk of cardiovascular events for allopurinol users when compared with non‐ULT users [adjusted hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.95–1.26] and the non‐ULT group with urate >6 mg dl−1 (adjusted HR 1.07, 95% CI 0.89–1.28). Within the allopurinol use cohort, cardiovascular event rates were 74.0 (95% CI 61.9–86.1) per 1000 person years for the 100 mg group, 69.7 (49.6–89.8) for the 200 mg group and 47.6 (38.4–56.9) for the ≥300 mg group. Compared with low‐dose (100 mg) users, high‐dose (≥300 mg) users had significant reductions in the risk of cardiovascular events (adjusted HR 0.69, 95% CI 0.50–0.94) and mortality (adjusted HR 0.75, 95% CI 0.59–0.94). CONCLUSIONS Less than 50% of patients taking allopurinol reached target urate concentration. Higher doses of allopurinol were associated with better control of urate and lower risks of both cardiovascular events and mortality.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Guidelines recommend that the therapeutic goal of urate‐lowering therapy (ULT) is to achieve a urate concentration of ≤6 mg dl −1 . • High‐dose allopurinol is associated with reduced cardiovascular events and mortality in heart failure patients. WHAT THIS STUDY ADDS • Less than 50% of patients taking allopurinol reached target urate concentration. • Higher doses of allopurinol were associated with better control of urate and lower risks of both cardiovascular events and mortality in all patients on allopurinol treatment. AIMS To characterize patients with urate measurements by urate‐lowering therapy (ULT) use and to study the impact of allopurinol treatment on cardiovascular and mortality outcomes. METHODS A cohort study using a record‐linkage database. The study included 7135 patients aged ≥60 years with urate measurements between 2000 and 2002 followed up until 2007. A Cox regression model was used. The association between urate levels, dispensed allopurinol and cardiovascular hospitalization and mortality was determined. RESULTS Six thousand and forty‐two patients were not taking ULT and 45.9% of those (2774 of 6042) had urate concentrations ≤6 mg dl −1 . Among 1035 allopurinol users, 44.7% (45.6% for men and 43.3% for women) reached target urate concentration. There was no significant increased risk of cardiovascular events for allopurinol users when compared with non‐ULT users [adjusted hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.95–1.26] and the non‐ULT group with urate >6 mg dl −1 (adjusted HR 1.07, 95% CI 0.89–1.28). Within the allopurinol use cohort, cardiovascular event rates were 74.0 (95% CI 61.9–86.1) per 1000 person years for the 100 mg group, 69.7 (49.6–89.8) for the 200 mg group and 47.6 (38.4–56.9) for the ≥300 mg group. Compared with low‐dose (100 mg) users, high‐dose (≥300 mg) users had significant reductions in the risk of cardiovascular events (adjusted HR 0.69, 95% CI 0.50–0.94) and mortality (adjusted HR 0.75, 95% CI 0.59–0.94). CONCLUSIONS Less than 50% of patients taking allopurinol reached target urate concentration. Higher doses of allopurinol were associated with better control of urate and lower risks of both cardiovascular events and mortality.
To characterize patients with urate measurements by urate-lowering therapy (ULT) use and to study the impact of allopurinol treatment on cardiovascular and mortality outcomes. A cohort study using a record-linkage database. The study included 7135 patients aged ≥60 years with urate measurements between 2000 and 2002 followed up until 2007. A Cox regression model was used. The association between urate levels, dispensed allopurinol and cardiovascular hospitalization and mortality was determined. Six thousand and forty-two patients were not taking ULT and 45.9% of those (2774 of 6042) had urate concentrations ≤6 mg dl(-1) . Among 1035 allopurinol users, 44.7% (45.6% for men and 43.3% for women) reached target urate concentration. There was no significant increased risk of cardiovascular events for allopurinol users when compared with non-ULT users [adjusted hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.95-1.26] and the non-ULT group with urate >6 mg dl(-1) (adjusted HR 1.07, 95% CI 0.89-1.28). Within the allopurinol use cohort, cardiovascular event rates were 74.0 (95% CI 61.9-86.1) per 1000 person years for the 100 mg group, 69.7 (49.6-89.8) for the 200 mg group and 47.6 (38.4-56.9) for the ≥300 mg group. Compared with low-dose (100 mg) users, high-dose (≥300 mg) users had significant reductions in the risk of cardiovascular events (adjusted HR 0.69, 95% CI 0.50-0.94) and mortality (adjusted HR 0.75, 95% CI 0.59-0.94). Less than 50% of patients taking allopurinol reached target urate concentration. Higher doses of allopurinol were associated with better control of urate and lower risks of both cardiovascular events and mortality.
Author Chen, Yang
Struthers, Allan D.
MacDonald, Thomas M.
Mackenzie, Isla S.
Wei, Li
Author_xml – sequence: 1
  givenname: Li
  surname: Wei
  fullname: Wei, Li
– sequence: 2
  givenname: Isla S.
  surname: Mackenzie
  fullname: Mackenzie, Isla S.
– sequence: 3
  givenname: Yang
  surname: Chen
  fullname: Chen, Yang
– sequence: 4
  givenname: Allan D.
  surname: Struthers
  fullname: Struthers, Allan D.
– sequence: 5
  givenname: Thomas M.
  surname: MacDonald
  fullname: MacDonald, Thomas M.
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ContentType Journal Article
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Issue 4
Keywords Hypouricemic agent
Prognosis
Enzyme
Allopurinol
Mortality
cardiovascular event
Enzyme inhibitor
Cardiovascular disease
Pyrazolopyrimidine derivatives
urate
Xanthine oxidase
Oxidoreductases
Circulatory system
Language English
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2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.
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Snippet WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Guidelines recommend that the therapeutic goal of urate‐lowering therapy (ULT) is to achieve a urate concentration...
To characterize patients with urate measurements by urate-lowering therapy (ULT) use and to study the impact of allopurinol treatment on cardiovascular and...
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SubjectTerms Aged
Aged, 80 and over
allopurinol
Allopurinol - therapeutic use
Biological and medical sciences
Cardiovascular Diseases - etiology
Cardiovascular Diseases - mortality
cardiovascular event
Cohort Studies
Female
Gout - complications
Gout - drug therapy
Gout - mortality
Gout Suppressants - therapeutic use
Hospitalization - statistics & numerical data
Humans
Hyperuricemia - complications
Hyperuricemia - drug therapy
Hyperuricemia - mortality
Male
Medical sciences
mortality
Pharmacoepidemiology
Pharmacology. Drug treatments
Proportional Hazards Models
Risk Factors
Time Factors
Treatment Outcome
United Kingdom
urate
Uric Acid - analysis
Title Impact of allopurinol use on urate concentration and cardiovascular outcome
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