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Current Rheumatology Reports

, 21:48 | Cite as

Cardiovascular Safety of Urate Lowering Therapies

  • Eun Ha Kang
  • Seoyoung C. Kim
Crystal Arthritis (L Stamp, Section Editor)
  • 312 Downloads
Part of the following topical collections:
  1. Topical Collection on Crystal Arthritis

Abstract

Purpose of Review

The effect of urate lowering treatment (ULT) on cardiovascular (CV) risk and mortality in gout has been a topic of interest. This review discusses the CV effect of ULT and comparative CV safety among ULT agents.

Recent Findings

The mechanism linking gout with CV risk is not fully understood but seems multifactorial involving hyperuricemia, xanthine oxidase (XO), oxidative stress, and chronic inflammation. Conflicting data exist regarding CV benefits of ULT in adults with and without hyperuricemia. Although meta-analyses on randomized controlled trials (RCTs) suggest CV benefits with allopurinol, few high-quality RCTs have examined the CV effect of ULT among patients with hyperuricemia or gout. The recent CARES trial adds new information on comparative CV safety between two XO inhibitors (XOIs), febuxostat and allopurinol, in patients with gout.

Summary

It remains unclear whether ULT reduces CV risk in patients with gout or hyperuricemia. Comparative CV safety studies of XOIs suggest that additional mechanisms beyond urate-lowering effect or XO inhibition are likely involved in CV risk modification in patients with gout. Ongoing RCTs of ULT may be able to further determine the effect of ULT on CV risk.

Keywords

Gout, hyperuricemia Cardiovascular Urate lowering treatment Allopurinol Febuxostat 

Notes

Compliance with Ethical Standards

Conflict of Interest

Seoyoung C. Kim has received research grants to the Brigham and Women’s Hospital from Roche, Pfizer, AbbVie, and Bristol-Myers Squibb for unrelated topics.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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    •• MacDonald TM, Ford I, Nuki G, Mackenzie IS, De Caterina R, Findlay E, et al. Protocol of the Febuxostat versus Allopurinol Streamlined Trial (FAST): a large prospective, randomised, open, blinded endpoint study comparing the cardiovascular safety of allopurinol and febuxostat in the management of symptomatic hyperuricaemia. BMJ Open. 2014;4(7):e005354. This is an ongoing randomized controlled trial in Europe to compare the CV risk between allopurinol and febuxostat among patients with gout. The study results may be able to provide further information related to the safety results from the CARES trial. PubMedPubMedCentralGoogle Scholar
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    • Kim SC, Neogi T, Kang EH, Liu J, Desai RJ, Zhang M, et al. Cardiovascular risks of probenecid versus allopurinol in older patients with gout. J Am Coll Cardiol. 2018;71(9):994–1004. This is the first population-based cohort study that compared the CV risk between probenecid and allopurinol users enrolled in the US Medicare. Consistent with unique beneficial effects on CV system by probenecid, the study showed a reduced CV risk associated with probenecid compared to allopurinol. However, there is a concern for a possible residual confounding particularly due to different renal status between the two treatment groups. PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Eun Ha Kang
    • 1
  • Seoyoung C. Kim
    • 2
    • 3
  1. 1.Division of Rheumatology Department of Internal MedicineSeoul National University Bundang HospitalSeongnamSouth Korea
  2. 2.Division of Rheumatology, Immunology and Allergy, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  3. 3.Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA

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