T2T strategy in gout lowers cardiovascular risk

A real-world data analysis from English and Swedish healthcare records reveals that a treat-to-target (T2T) approach in urate-lowering therapy (ULT) modestly but significantly reduces the risk of major adverse cardiovascular events (MACE) in patients with gout.

“We and others have previously described the associations of gout flares and subsequent cardiovascular events,” said Dr Edoardo Cipolletta (Polytechnic University of Marche, Italy) [1]. 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 patients from 2 major European cohorts, the UK CPRD Aurum and Sweden’s VEGA database.

Patients were classified into 2 groups: those achieving the serum urate target of <360 µmol/L urate within 12 months of ULT initiation (T2T-ULT) and those who did not (fire-and-forget). Patients in the fire-and-forget arm had either not any recorded SU measurements within 12 months after ULT initiation, or they had persistent SU levels >360 µmol/l in the 12 months after ULT initiation. 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 in the UK and 2.62 years in the Swedish cohort, 13.77% (n=15,081) of UK patients and 15.97% (n=1,120) of Swedish patients 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 patients treated with the T2T strategy. Interestingly, there was an interaction between age and ULT strategies, as the effect size in people aged >65 years was significantly greater than in younger patients (P=0.02).

Furthermore, 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. 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 data. OP0005, EULAR 2025, 11–14 June, Barcelona, Spain.

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Posted on 20 June 2025