medwireNews: Meeting the serum urate target of below 360 µmol/L within a year of initiating urate-lowering treatment (ULT) may significantly lower the risk for major adverse cardiovascular events (MACE) in people with gout, suggests research.
Edoardo Cipolletta (University of Nottingham, UK), who presented the findings at the EULAR 2025 Congress in Barcelona, Spain, said that “the effect size is quite modest,” but the benefit comes at no additional harm or cost for patients or national healthcare systems “since this is already the recommended treatment strategy.”
He continued: “Therefore, this is additional evidence supporting the usefulness and validity of this approach that extends beyond the joints.”
Outlining the rationale for the study, Cipolletta said that gout flares are known to be associated with subsequent cardiovascular events, and as treat-to-target ULT reduces the number of gout flares, the investigators asked whether it would also affect the CV risk.
They drew on two primary care databases – the UK Clinical Practice Research Datalink (CPRD) Aurum and Western Sweden Regional Healthcare Database (VEGA) – to identify adults with a new diagnosis of gout who initiated ULT during 2007–2021 and 2007–2017, respectively.
Of the 109,504 participants in CPRD Aurum, 29,919 achieved serum urate levels below 360 µmol/L within 12 months of starting treatment, as did 1551 of the 7014 VEGA participants.
“We performed an emulated target trial using a cloning, censoring, and weighting approach to minimize immortal time bias, lead time bias, and survivor bias related to the lack of alignment between the start of follow-up and the assignment of the treatment strategy,” explained the presenter.
In the UK dataset, the primary endpoint of the first MACE (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) in the 5 years following ULT initiation occurred in 11,651 patients who achieved the serum urate target and 12,790 of those who either did not or for whom serum urate measurements were not available.
The weighted 5-year MACE-free survival rates were 89.4% and 88.0%, respectively, equating to an absolute difference between the groups of 1.4 percentage points and a significant weighted hazard ratio (HR) for MACE of 0.88 in favor of the treat-to-target approach.
The findings were similar in the Swedish dataset, with 5-year MACE-free survival rates of 76.8% and 75.5% in the treat-to-target and control groups, respectively. The absolute between-group difference was 1.3 percentage points and the weighted HR was 0.94.
Cipolletta pointed out that “the results in the Swedish dataset had wider confidence intervals due to the lower sample size and also lower absolute survival rates due to an older population with more comorbidities.”
He added that the association was consistent regardless of prior cardiovascular diseases, for secondary outcomes such as MACE requiring hospitalization or leading to death, and in sensitivity analyses that excluded patients without serum urate measurements and censored the follow-up on the date of ULT discontinuation.
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