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Treat-to-Target Urate-Lowering Treatment and Cardiovascular Outcomes in Patients With Gout
Edoardo Cipolletta1,2, Tatiana Zverkova Sandström3, Davide Rozza4
1Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom.
Insights
Achieving a serum urate target below 6 mg/dL with urate-lowering treatment (ULT) significantly reduced cardiovascular events in gout patients. Lowering urate levels further, to below 5 mg/dL, offered even greater protection against major adverse cardiovascular events.
Area of Science:
- Cardiology
- Rheumatology
- Clinical Research
Background:
- Gout is linked to increased cardiovascular disease (CVD) risk.
- The benefit of achieving specific serum urate targets with urate-lowering treatment (ULT) on cardiovascular outcomes in gout patients remains unclear.
Purpose of the Study:
- To assess the association between achieving a serum urate target below 6 mg/dL and cardiovascular events in gout patients initiating ULT.
- To evaluate the impact of ULT adherence to a treat-to-target (T2T) strategy on cardiovascular risk.
Main Methods:
- A new-user cohort study utilizing an emulated target trial framework.
- Data from UK primary care records (CPRD Aurum) linked to hospitalization and mortality records (2007-2021).
- Patients with gout newly prescribed ULT and pretreatment serum urate >6 mg/dL were followed for up to 5 years.
Main Results:
- Over 109,000 patients were analyzed; 27.3% were in the T2T ULT arm (serum urate <6 mg/dL within 12 months).
- The T2T ULT group showed a 1.0% higher 5-year survival and a reduced risk of major adverse cardiovascular events (HR, 0.91).
- Achieving a lower target (<5 mg/dL) demonstrated a larger risk reduction (HR, 0.77). Negative control outcomes showed no differences.
Conclusions:
- Achieving serum urate levels below 6 mg/dL within 12 months of starting ULT is associated with reduced 5-year cardiovascular risk in gout patients.
- The cardiovascular benefits were more pronounced for patients with higher baseline cardiovascular risk.
- A more stringent target (<5 mg/dL) yielded greater cardiovascular risk reduction.
Importance:
Gout is associated with increased cardiovascular risk. Whether achieving a target serum urate level lower than 6 mg/dL with urate-lowering treatment (ULT) would reduce cardiovascular risk in patients with gout is unknown.
Objectives:
To evaluate the association between achieving a serum urate treatment target lower than 6 mg/dL and cardiovascular events among patients with gout who were newly prescribed ULT.
Design, Setting, And Participants:
This new-user cohort study using emulated target trial framework with up to 5-year follow-up was performed using primary care data from the Clinical Practice Research Datalink Aurum linked to hospitalization and mortality records from January 1, 2007, to March 29, 2021. Patients were 18 years or older, diagnosed with gout, had a pretreatment serum urate level higher than 6 mg/dL, and were newly prescribed ULT. Data were analyzed from May 2024 to January 2025.
Exposure:
Patients were assigned to the treat-to-target (T2T) ULT arm or the non-T2T ULT arm if they achieved or did not achieve a serum urate level lower than 6 mg/dL, respectively, within 12 months of their first ULT prescription.
Main Outcomes And Measures:
The primary outcome was first major adverse cardiovascular event within 5 years of first ULT prescription. Gout flare was the positive control outcome. Acute bronchitis, cataract, and appendicitis were included as negative control outcomes. Weighted absolute 5-year event-free survival and weighted hazard ratios (HRs) with 95% CIs were estimated.
Results:
Of 109 504 patients included, the mean (SD) age was 62.9 (15.2) years, 22.2% were female, the mean (SD) disease duration was 2.5 (3.6) years, and 27.3% were included in the T2T ULT arm. Patients in the T2T ULT arm had a higher 5-year survival (weighted survival difference, 1.0%; 95% CI, 0.5%-1.6%) and lower risk of major adverse cardiovascular events (weighted HR, 0.91; 95% CI, 0.89-0.92) than those in the non-T2T ULT arm. There was a greater association for people at high and very high cardiovascular risk than those with moderate risk. Patients who achieved a lower serum urate target of less than 5 mg/dL had a larger risk reduction (weighted survival difference, 2.6%; 95% CI, 0.9%-3.6%; weighted HR, 0.77; 95% CI, 0.72-0.81). Patients in the T2T ULT arm had fewer gout flares. No differences were observed for negative control outcomes.
Conclusions And Relevance:
In this cohort study among patients with gout who were newly prescribed ULT, achieving serum urate levels lower than 6 mg/dL within 12 months was associated with a lower 5-year risk of major adverse cardiovascular events.
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