Achieving guideline-recommended serum urate levels after starting urate-lowering therapy (ULT) for gout is associated with a lower five-year risk of major adverse cardiovascular events (MACE), a large new-user cohort study has found.

Gout has long been associated with excess cardiovascular risk, but whether achieving recommended serum urate targets mitigates this risk has remained uncertain.

This large observational study, published in JAMA Internal Medicine, therefore aimed to evaluate the association between a treat-to-target (T2T) ULT strategy and cardiovascular outcomes in patients with gout who had been newly prescribed ULT.

The international research team, led by investigators from the University of Nottingham, used an emulated target trial framework and analysed routinely collected primary care data from the Clinical Practice Research Datalink Aurum, which was linked to hospitalisation and mortality records in England.

Gout and MACE

The study included 109,504 adults aged 18 years or older with a new diagnosis of gout, a pretreatment serum urate level above 6 mg/dL and a first prescription for ULT between 2007 and 2021.

The mean age was 62.9 years, 22.2% were female, and the mean gout duration before ULT initiation was 2.5 years. Almost all patients (99.2%) were prescribed allopurinol.

Patients were classified into a T2T group if they achieved a serum urate level below 6 mg/dL within 12 months of starting ULT, or a non-T2T group if they did not. Overall, 27.3% achieved the target within 12 months.

Over a mean follow-up of 3.45 years, 13.8% of patients experienced a MACE, defined as non-fatal myocardial infarction, non-fatal stroke or cardiovascular death.

After weighting for confounders, patients in the T2T group had higher five-year event-free survival than those in the non-T2T group (89.4% vs 88.3%), corresponding to an absolute survival difference of 1.0%.

Achieving the target was associated with a lower risk of MACE (weighted hazard ratio 0.91). The association was stronger in patients at high or very high baseline cardiovascular risk and in those achieving a more stringent serum urate level below 5 mg/dL, who showed a 2.6% absolute survival benefit and a hazard ratio of 0.77.

Fewer gout flares were also observed in the T2T group, while no associations were seen for negative control outcomes.

Statistically significant reduction in five-year cardiovascular risk

The authors noted several limitations, including the observational design, potential residual confounding, incomplete reporting of gout flares and possible misclassification of serum urate exposure. However, extensive adjustment, sensitivity analyses and the use of negative control outcomes supported the internal validity of the findings.

The study concluded that achieving serum urate levels below 6 mg/dL within 12 months of starting ULT was associated with a statistically significant reduction in five-year cardiovascular risk. This highlights T2T urate lowering as an important clinical strategy in gout management, particularly in patients with high cardiovascular risk

The authors have now called for further research to clarify the biological mechanisms underpinning their observed association.

Reference
Cipolletta E et al. Treat-to-Target Urate-Lowering Treatment and Cardiovascular Outcomes in Patients With Gout. JAMA Intern Med 2026; Jan 26:e257453.