Cardiovascular Safety of Urate Lowering Therapies.

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. 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.