Reaching target serum urate level linked to lower MACE risk in people with gout

medwireNews: People with gout who achieve a serum urate treatment target below 6.0 mg/dL have a significantly lower 5-year risk for major adverse cardiovascular events (MACE) than those who do not, research suggests.

The findings are the result of an emulated target trial that included data for 109,504 individuals (mean age 63 years, 78% men) with gout who were prescribed urate-lowering treatment (ULT), most commonly allopurinol (99.2%), for the first time between 2007 and 2021.

At baseline, the mean serum urate level was 8.6 mg/dL. After 1 year of treatment, 27.3% of participants achieved the treat to target level of less than 6.0 mg/dL, with a mean level of 5.2 mg/dL, compared with 7.7 mg/dL in the group who did not reach the target level.

Abhishek Abhishek (University of Nottingham, UK) and co-authors report in JAMA Internal Medicine that individuals who reached the serum urate target had a significant 9% lower risk for MACE (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular [CV] death) than those who did not, with 5-year weighted MACE-free survival rates of 89.4% and 88.3%, respectively.

“Although the absolute risk reduction was modest, the potential population-level benefit is substantial, as 55.8 million people globally had gout in 2020, and this is expected to rise to 95.8 million by 2050,” Abhishek et al remark.

The magnitude of MACE risk reduction was greater among patients who achieved a serum urate target of less than 5 mg/dL, at 23%, relative to those with a higher serum urate level. At this target level, the 5-year weighted MACE-free survival rates were 90.9% and 88.3%, respectively.

When the researchers stratified the patients by baseline CV risk, they found that individuals with high and very high CV risk, according to European CV risk categories, had significant 12% and 9% lower rates for MACE, respectively, if they achieved the ULT 6.0 mg/dL target versus if they did not. By comparison, reaching this standard ULT target did not significantly impact MACE risk in individuals with moderate baseline CV risk.

Abhishek and co-investigators also note that patients who achieved the standard ULT target had a significant 3% lower risk for gout flares than those who did not.

They suggest that the association between reaching the ULT target and MACE risk “is likely to be mediated by fewer gout flares, as the control of hyperuricemia by itself is not expected to prevent cardiovascular diseases given the findings of several genetic studies and the ALL-HEART trial.”

The authors conclude: “Future studies (eg, with high-quality data about gout flares) are needed to better understand the mechanism underpinning the observed association.”

New strategies necessary to improve gout management

In an accompanying comment, Pascal Richette and colleagues, from Université Paris Cité in France, say that the results “should profoundly change the perception of gout management” and “suggest a dual benefit of optimal SU [serum urate] control: fewer gout flares and fewer cardiovascular events.”

However, they add that the “encouraging findings are nevertheless challenged by a worrisome reality: only 27.3% of patients initiating ULT in this study achieved [serum urate] levels below 6 mg/dL within 12 months.”

The authors continue: “Such misuse of ULT not only perpetuates uncontrolled disease activity, but may also prevent patients from benefiting from the potential cardiovascular protection associated with optimal [serum urate] control.”

Richette et al conclude: “New strategies and care models are therefore urgently needed to improve the management of gout. 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.”

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JAMA Intern Med 2026; doi:10.1001/jamainternmed.2025.7453
JAMA Intern Med 2026; doi:10.1001/jamainternmed.2025.7459