Key Clinical Summary

• In a cohort of 109,504 adults with gout newly prescribed urate-lowering treatment (ULT), 27.3% achieved a serum urate level below 6 mg/dL within 12 months.
• Target achievement was associated with fewer major adverse cardiovascular events over 5 years than nonachievement (weighted hazard ratio, 0.91; 95% CI, 0.89–0.92).
• The association was greater among patients at high or very high cardiovascular risk. The study assessed an association, not whether reaching the target caused the difference.

A serum urate level below 6 mg/dL within 12 months of starting urate-lowering treatment (ULT) was associated with a lower 5-year risk of major adverse cardiovascular events among adults with gout, according to a cohort study published in JAMA Internal Medicine. Investigators used primary care data linked to hospitalization and mortality records to compare patients who achieved the treatment target with those who did not.

Study Findings

The new-user cohort study used an emulated target trial framework and included 109,504 adults diagnosed with gout. All had a pretreatment serum urate level above 6 mg/dL and were newly prescribed ULT. Records covered January 1, 2007, through March 29, 2021; follow-up extended to 5 years after the first prescription.

Patients were assigned to the treat-to-target group if they reached a serum urate level below 6 mg/dL within 12 months. Those who did not reach that level formed the comparison group. The cohort’s mean age was 62.9 years, 22.2% were female, and mean gout duration was 2.5 years. Overall, 27.3% were in the treat-to-target group.

Compared with the non–treat-to-target group, patients who reached the target had higher weighted 5-year event-free survival, with a difference of 1.0 percentage point (95% CI, 0.5–1.6), and a lower risk of major adverse cardiovascular events (weighted hazard ratio, 0.91; 95% CI, 0.89–0.92).

The association was greater for patients at high or very high cardiovascular risk than for those at moderate risk. Among patients who achieved a serum urate level below 5 mg/dL, the weighted survival difference was 2.6 percentage points (95% CI, 0.9–3.6), and the weighted hazard ratio was 0.77 (95% CI, 0.72–0.81).

Clinical Implications

The findings add cardiovascular outcomes to the questions clinicians may consider when assessing serum urate targets in gout care. They show an association between reaching a level below 6 mg/dL after starting ULT and subsequent cardiovascular events; the cohort design does not establish that target achievement caused the lower event risk.

Patients in the treat-to-target group also had fewer gout flares, which investigators designated as a positive control outcome. They found no differences in the negative control outcomes of acute bronchitis, cataract, or appendicitis. These results accompany the cardiovascular analysis but do not change its observational nature.

The study does not report a randomized comparison of urate targets or determine which part of the observed cardiovascular difference, if any, resulted from ULT itself. Its stated conclusion is limited to the association between achieving the target within 12 months and lower 5-year cardiovascular risk. Further research would be needed to determine whether reaching that target reduces cardiovascular risk.

Reference: Cipolletta E, Zverkova Sandström T, Rozza D. Treat-to-target urate-lowering treatment and cardiovascular outcomes in patients with gout. JAMA Intern Med. 2026;186(3):332-342. doi:10.1001/jamainternmed.2025.7453