Fewer than one-third of patients with gout achieved recommended serum urate targets within 12 months, and achievement of this target was associated with a 9% relative risk reduction for major adverse cardiovascular events, according to a recent study.
In a large population-based analysis emulating a target trial, achieving serum urate levels lower than 6 mg/dL within 12 months of urate-lowering treatment (ULT) initiation was associated with higher 5-year cardiovascular event–free survival and a reduced risk of major adverse cardiovascular events (MACE) among patients with gout. The association was strongest among patients with high or very high baseline cardiovascular risk, and achieving a more stringent serum urate level lower than 5 mg/dL was associated with a 23% relative risk reduction.
The study included 109,504 adults in England with newly diagnosed gout who initiated ULT between January 1, 2007, and March 29, 2021, using linked primary care, hospitalization, and mortality data from the Clinical Practice Research Datalink Aurum. The mean age was 63 years, 22% of patients were female, and the mean pretreatment serum urate level was 8.6 mg/dL. Overall, 27% of patients achieved the serum urate target within 12 months, with 80% of those achieving target doing so within 6 months. Nearly all patients (99%) were prescribed allopurinol. Patients were followed for up to 5 years, with a mean follow-up of 3.5 years, during which 14% experienced a MACE.
The researchers used an emulated target trial framework with a new-user design and a cloning, censoring, and weighting approach to reduce immortal time bias. Weighted survival analyses adjusted for demographic and socioeconomic factors, cardiovascular risk factors, comorbidities, gout severity measures, medication use, and adherence to ULT. The weighted 5-year cardiovascular event–free survival was 89% in the treat-to-target group and 88% in the non–treat-to-target group, yielding an absolute survival difference of 1%. Among patients who achieved serum urate levels lower than 5 mg/dL, the absolute 5-year survival difference was 2.6%. Treat-to-target therapy was also associated with fewer gout flares, while no associations were observed for negative control outcomes, including acute bronchitis, cataract, and appendicitis.
Several limitations should be noted. As an observational study, residual confounding cannot be fully excluded despite extensive covariate adjustment and the use of negative control outcomes. Inclusion of patients with prior cardiovascular events may have introduced surveillance bias, although findings were consistent in analyses restricted to first-ever cardiovascular events. Exposure misclassification was possible because serum urate levels were not measured in all patients during the first 12 months, and some patients in the non–treat-to-target group may have achieved target levels after this period, which would likely bias results toward the null. In addition, gout flares are incompletely captured in routine care data, limiting mechanistic interpretation, and changes in comorbidities, lifestyle factors, or treatments during follow-up may have contributed to residual confounding.
"Given the high cardiometabolic burden in gout, this is an important reason for prescribing ULT using a treat-to-target approach," wrote lead study author Edoardo Cipolletta, PhD, of the University of Nottingham, and colleagues.
Disclosures can be found in the study.
Source: JAMA Internal Medicine
