Treat-to-target ULT approach reduces cardiac risk in gout patients

Treating gout patients with urate-lowering therapy (ULT) to meet a serum urate level below 6 mg/dL within 12 months results in a reduced risk of major adverse cardiovascular events (MACE), as shown in a new user cohort study.

The weighted MACE-free survival rates at 5 years were 89.4 percent among those who achieved the target serum urate level within 12 months (treat-to-target arm) and 88.3 percent among those who did not (control arm) (survival difference, 1 percent, 95 percent confidence interval [CI], 0.5–1.6). Achieving the target serum urate level was associated with a 9-percent reduction in the risk of MACE (weighted hazard ratio [HR], 0.91, 95 percent CI, 0.89–0.92). [JAMA Intern Med 2026;doi:10.1001/jamainternmed.2025.7453]

Notably, a larger risk reduction was seen for patients who achieved a serum urate level lower than 5 mg/dL (5-year weighted MACE-free survival difference, 2.6 percent, 95 percent CI, 0.9–3.6; weighted HR, 0.77, 95 percent CI, 0.72–0.81).

Results were consistent for secondary outcomes, with the treat-to-target arm having lower risks of myocardial infarction (weighted HR, 0.88, 95 percent CI, 0.85–0.90), stroke (weighted HR, 0.86, 95 percent CI, 0.83–0.90), MACE requiring hospitalization or leading to death (weighted HR, 0.87, 95 percent CI, 0.84–0.89), and first-ever MACE (weighted HR, 0.90, 95 percent CI, 0.88–0.92).

Additionally, fewer gout flares occurred in the treat-to-target arm than in the control arm, with a weighted incidence rate ratio of 0.97 (95 percent CI, 0.95–0.99).

Further analysis indicated that the protective association between achieving serum urate levels below 6 mg/dL and MACE risk was more pronounced for patients with high/very high baseline cardiovascular risk vs those with moderate risk. The association was not modified by either age or sex.

In light of the findings, the investigators emphasized that ULT should be prescribed using a treat-to-target approach, given the high cardiometabolic burden in gout.

“Although the absolute MACE risk reduction was modest, the potential population-level benefit is substantial,” as the number of people with gout globally is expected to rise from 55.8 million in 2020 to 95.8 million by 2050, they added. [Lancet Rheumatol 2024;6:e507-e517]

Expanded benefit

“So far, the main benefit of a treat-to-target urate-lowering strategy has been the reduction and, ultimately, the disappearance of gout flares… The [present] study … now extends these benefits [to include cardiovascular outcomes, which] should profoundly change the perception of gout management,” noted Drs Pascal Richette, Augustin Latourte, and Hang-Korng Ea, all from Paris Cité University, Paris, France, in an accompanying editorial. [JAMA Intern Med 2026;doi:10.1001/jamainternmed.2025.7459]

“These new data suggest that a lower threshold may also yield extra-articular benefits, potentially reinforcing the case for a more ambitious target across all patients with gout—one that would promote faster dissolution of pathogenic urate crystals,” Richette and colleagues continued.

But meeting the serum urate target to see the benefits can be a challenge for some patients, they said, noting that only 27.3 of patients initiating ULT in the study achieved serum urate levels below 6 mg/dL within 12 months.

“New strategies and care models are therefore urgently needed to improve the management of gout,” according to Richette and colleagues. “Efforts should focus on enhancing adherence to ULT—possibly by helping patients visualize the dissolution of their urate deposits when therapy is effective (ie, the treat-to-dissolve strategy)—and, above all, on determining the optimal serum urate target needed to both prevent flares and reduce cardiovascular events.”

Study population

The study included 109,504 gout patients (mean age 62.9 years, 77.8 percent male, 85.7 percent White, mean disease duration 2.5 years) who were newly initiating ULT. Allopurinol was the most common prescription (99.2 percent), and most patients were started on a low dose (82.4 percent).

A total of 27.3 percent of patients achieved the target serum urate level within 12 months of treatment and were included in the treat-to-target arm. The mean serum urate level at the first year of follow-up was 5.18 mg/dL in the treat-to-target arm and 7.73 mg/dL in the control arm, which corresponded to a mean decrease of 3.17 and 1.18 mg/dL from baseline in the respective treatment arms.