Targeting serum uric acid pays off: gout strategy cuts MACE

Evidence from English and Swedish registries confirms that achieving uric acid targets through a treat-to-target (T2T) urate-lowering therapy (ULT) is associated with a modest yet meaningful reduction in cardiovascular events among patients with gout. In addition, these patients showed a higher 5-year major adverse cardiovascular event (MACE)-free survival.

Gout flares were associated with subsequent cardiovascular events [1,2]. “We and others have previously described the associations of gout flares and subsequent cardiovascular events,” said Dr Edoardo Cipolletta (Polytechnic University of Marche, Italy) [3]. His study aimed to evaluate the impact of achieving a serum urate treatment target of <360 μmol/L within the first year of treatment on the 5-year risk of MACE among patients with gout and newly prescribed ULT. The study included 116,518 participants from 2 major European cohorts, the UK CPRD Aurum and Sweden’s VEGA database.

Participants were classified into 2 groups: those achieving the serum urate target of <360 µmol/L within 12 months of ULT initiation (T2T-ULT) and those who did not (fire-and-forget). Participants in the fire-and-forget arm had either no recorded serum urate measurements within 12 months after ULT initiation or had persistent serum urate levels >360 µmol/L. All participants were matched for 40 baseline covariates, including demographics, cardiovascular risk factors, and gout characteristics. The primary endpoint was the 5-year risk of MACE, defined as non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death.

During a mean follow-up time of 3.45 years in the UK and 2.62 years in the Swedish cohort, 13.77% (n=15,081) of UK participants and 15.97% (n=1,120) of Swedish participants experienced a MACE.

In the UK cohort, the 5-year weighted MACE-free survival was 89.43% (95% CI 88.97–89.89) in the T2T-ULT group versus 88.03% (95% CI 87.73–88.33) in the comparator group, corresponding to a hazard ratio (HR) of 0.88 (95% CI 0.86– 0.89). In the Swedish VEGA-cohort, corresponding survival rates were 76.82% (95% CI 74.03–79.61) and 75.50% (95% CI 73.99–77.601), with an HR of 0.94 (95% CI 0.84–1.04).

A pooled analysis confirmed a higher 5-year MACE-free survival and a relative risk reduction of 6% to 11% in participants treated with the T2T strategy. Interestingly, an interaction between age and ULT strategies was observed, as the effect size in people aged >65 years was significantly greater than in younger patients (P=0.02). As expected, achieving the serum urate target was associated with fewer gout flares (IRR 0.95; 95% CI 0.92–0.99).

“The effect size is quite modest, but no additional harm exists for patients since this is already the recommended treatment strategy. The results support the usefulness and the validity of the T2T approach that extends beyond the joints,” Dr Cipolletta concluded.

1. Cipolletta E, et JAMA. 2022;328:440-450.
2. Lopez D, et ACR Open Rheumatol. 2023;5:298–304.
3. Cipolletta E. Cardiovascular outcomes of treat-to-target versus fire-and-forget urate-lowering treatment in gout: emulated target trial studies using linked English and Swedish primary care, hospitalisation and mortality OP0005, EULAR 2025, 11–14 June, Barcelona, Spain.

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Posted on 8 August 202525 August 2025