Related Experiment Video
Updated: Mar 27, 2026
A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
Published on: November 7, 2017
Impact of Urate Level on Cardiovascular Risk in Allopurinol Treated Patients. A Nested Case-Control Study
Kasper Søltoft Larsen1,2, Anton Pottegård1, Hanne M Lindegaard2
1Clinical Pharmacology, Department of Public Health, University of Southern Denmark, JB Winsloewvej 19.2, DK-5000, Odense C, Denmark.
Insights
Achieving target urate levels with allopurinol did not reduce cardiovascular events in gout patients. Higher allopurinol doses may be needed for cardiovascular risk reduction, or the effect may not depend on urate levels.
Area of Science:
- Rheumatology
- Cardiology
- Pharmacology
Background:
- Gout increases cardiovascular event risk.
- Urate-lowering drugs like allopurinol may reduce this risk.
- The target urate level for cardiovascular risk reduction is unknown.
Purpose of the Study:
- To investigate if achieving target plasma urate levels with allopurinol impacts cardiovascular outcomes.
- Study conducted in long-term allopurinol users.
Main Methods:
- Case-control study nested within a cohort of allopurinol users.
- Compared cardiovascular event cases with controls based on reaching urate target (<0.36 mmol/l).
- Adjusted for confounders using prescription, lab, and contact data.
Main Results:
- No association found between target urate levels and cardiovascular events (aOR 1.01, 95% CI 0.79-1.28).
- No significant effect observed in subgroups (age, gender, renal function, dose, urate level).
- Allopurinol doses in the study were generally low (mean ≈ 140 mg/day).
Conclusions:
- Unable to demonstrate a link between achieved urate levels and cardiovascular risk with allopurinol.
- Higher allopurinol doses might be required for cardiovascular benefits.
- Allopurinol's cardiovascular effect may not be solely mediated by urate reduction.
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.
![Quantitative SERS Detection of Uric Acid via Formation of Precise Plasmonic Nanojunctions within Aggregates of Gold Nanoparticles and Cucurbit[n]uril](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F61682.jpg&w=3840&q=50)
Related Concept Videos
01:26Atherosclerosis III: Management
01:27Urinary Tract Calculi IV: Nutrition Therapy and Prevention
01:11Renal Failure: Dose Adjustments
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
01:17Factors Affecting Renal Clearance: Renal Impairment
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
01:18Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Metabolism