New Evidence Links Targeted Urate-Lowering to Cardiovascular Benefits in Gout
Gout is often managed as a painful joint disease, but it is also strongly associated with increased cardiovascular risk. A new study published in JAMA Internal Medicine suggests that achieving recommended serum urate targets after starting urate-lowering therapy (ULT) may reduce the risk of major cardiovascular events over time.
For clinicians who treat patients with gout, these findings shift the perspective on treat-to-target urate management from purely symptom control to a strategy that may have broader health implications.
A Rigorous Study Using Real-World Data
The study followed 109,504 adults with gout who were newly prescribed ULT, predominantly allopurinol. Researchers used a method called target trial emulation, an advanced observational approach designed to replicate the structure of a randomized controlled trial when an actual trial would be impractical or unethical.
Rather than comparing medications, patients were grouped based on whether they achieved a serum urate (SU) level below 6 mg/dL within 12 months of starting therapy. They were then followed for up to five years to evaluate the occurrence of major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular death.
Key Results to Know
Patients who achieved the urate target experienced a measurable reduction in cardiovascular events:
- Hazard ratio for MACE: 0.91 (9% relative risk reduction)
- Absolute 5-year event-free survival improvement: 1.0%
The association was even stronger among patients who achieved SU <5 mg/dL:
- Hazard ratio: 0.77 (23% relative risk reduction)
- Absolute survival difference: 2.6%
Notably, the benefit was greatest in patients with high and very high baseline cardiovascular risk.
What May Explain the Association
The authors suggest that the observed association is likely mediated by fewer gout flares in patients who successfully reach urate targets. Importantly, they note that control of hyperuricemia alone is not expected to prevent cardiovascular disease based on prior genetic studies and clinical trials. Instead, patients who achieve and maintain target urate levels experience fewer flares, which may be connected to the lower cardiovascular event rates observed.
Practical Implications for Clinicians
These findings reinforce the importance of an intentional, treat-to-target approach in gout management:
- Routinely monitoring serum urate after initiating ULT
- Titrating allopurinol or alternative agents beyond starting doses to reach target levels
- Reinforcing medication adherence, particularly in the first year of therapy
- Avoiding acceptance of subtherapeutic urate levels when patients remain above goal
Ensuring that patients achieve target urate levels may have implications beyond preventing joint symptoms.
Study Limitations
While the study provides compelling evidence, its observational nature means causality cannot be definitively established. Additionally, variations in patient adherence and lifestyle factors were not fully controllable.
The Takeaway
This large real-world study suggests that achieving serum urate targets after starting ULT is associated with a lower risk of major cardiovascular events. Treat-to-target urate control should be viewed as an important component of comprehensive gout management, with potential benefits that extend beyond flare prevention.
Source
- Cipolletta E, Zverkova Sandström T, Rozza D, Leyrat C, Nakafero G, Drivelegka P, Avery AJ, Mamas MA, Tata LJ, Dehlin M, Abhishek A. Treat-to-Target Urate-Lowering Treatment and Cardiovascular Outcomes in Patients With Gout. JAMA Intern Med. 2026 Jan 26:e257453. doi: 10.1001/jamainternmed.2025.7453. Epub ahead of print. PMID: 41587055; PMCID: PMC12836279.
