Cardiovascular safety risks associated with gout treatments

ABSTRACT

Introduction

Uric acid is the final byproduct of purine metabolism. The loss of the enzyme that hydrolyzes uric acid to allantoin was lost, leading to a decrease in uric acid excretion and its further accumulation. The buildup of uric acid leads to damage in different organ systems, including the cardiovascular system. With the increasing burden of cardiovascular disease worldwide, a growing body of evidence has addressed the relationship between urate, cardiovascular outcomes, and gout medication cardiovascular safety. Areas covered: We discuss the most common gout therapies used for the reduction of serum urate and management of gout flares in different observational and clinical trials and their effects on different aspects of cardiovascular disease. We selected the most representative clinical studies that evaluated cardiovascular outcomes with each gout therapy as well as recommendation given by the most representative guidelines from Rheumatology societies for the management of gout.

Expert opinion

The treatment of gout reduces joint damage and it can also lessen CV morbidity. Allopurinol shows CV safety profile when compared to other ULTs. Evidence supporting CV safety with the use of colchicine and IL-1 agents is promising and research needs to be conducted to further assess this outcome.

KEYWORDS:

• Gout
• cardiovascular disease
• gout flare
• uric acid

Article highlights

• Overall, most common gout therapies are generally safe. Allopurinol in particular appears to have some CV benefits and it is used as first line treatment for gout.

• Febuxostat CV safety concerns has led to its relegation to a second line urate-lowering therapy after allopurinol.

• Caution to prescribe Febuxostat has been suggested by most clinical guidelines for the management of gout.

• Pegloticase, though efficacious for refractory gout, has not yet been thoroughly evaluated for CV risk and might reduce blood pressure in gout patients.

• Colchicine, a commonly used drug for gout flares, has shown promising beneficial CV outcomes.

• Canakinumab, a drug experimentally used for gout flares has also shown promising CV benefits.

This box summarizes key points contained in the article.

Declaration of interest

K Saag has served as a consultant for Arthrosi, Atom Bioscience, Horizon, Inflazome, LG Pharma, Mallinkrodt and SOBI; and has received research grants from Horizon and Shanton. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A peer reviewer on this manuscript has disclosed that they have received grants from AMGEN and Pfizer, and have served on advisory boards for Johnson and Johnson and IFM. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.