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Cardiovascular effects of urate-lowering therapies in patients with chronic gout: a systematic review and
1Department of Rheumatology, Schulich School of Medicine & Dentistry, Western University of Canada, St Joseph Health Care, London, ON Canada.
Insights
Urate-lowering treatment (ULT) for gout does not appear to significantly reduce cardiovascular events based on current randomized trial data. More research is needed to confirm long-term cardiovascular safety and efficacy in high-risk gout patients.
Area of Science:
- Cardiology
- Rheumatology
- Clinical Trials
Background:
- Gout is a metabolic disorder characterized by hyperuricemia and deposition of monosodium urate crystals.
- Elevated uric acid levels are associated with increased cardiovascular (CV) risk.
- Urate-lowering treatments (ULTs) aim to reduce serum uric acid, but their impact on CV outcomes remains unclear.
Purpose of the Study:
- To evaluate the efficacy of urate-lowering treatment (ULT) in reducing cardiovascular (CV) outcomes in patients with gout.
- To synthesize evidence from randomized controlled trials (RCTs) investigating the CV safety of various ULTs.
Main Methods:
- A systematic search of randomized trials was conducted for ULTs used in gout management.
- Eligible trials reported CV safety data for ULTs, including allopurinol, febuxostat, and others.
- Pooled analysis was performed to compare CV event rates between different ULTs and placebo.
Main Results:
- Analysis of six trials with CV events showed no significant difference between febuxostat and allopurinol (RR 1.69; P=0.37).
- Comparing any ULT to placebo (eight studies) did not demonstrate a significant difference in CV events (RR 1.47; P=0.49) or all-cause mortality (RR 1.45; P=0.60).
- Long-term studies suggested a trend towards more CV events with febuxostat compared to allopurinol.
Conclusions:
- Current randomized controlled trial data do not indicate significant differences in CV events among various urate-lowering treatments for gout.
- Existing trials may be underpowered or too short to detect potential CV benefits or risks associated with ULTs.
- Further long-term studies are warranted to clarify the cardiovascular safety profile of ULTs in high-risk gout populations.
Objectives:
To determine if urate-lowering treatment (ULT) in gout can reduce cardiovascular (CV) outcomes.
Methods:
Randomized trials were searched for treatment with ULT in gout. Eligible trials had to report CV safety of a ULT. Potential medications included allopurinol, febuxostat, pegloticase, rasburicase, probenecid, benzbromarone, sulphinpyrazone, losartan, fenofibrate and sodium-glucose linked transporter 2 inhibitors.
Results:
A total of 3084 citations were found, with 642 duplicates. After the primary screen, 35 studies were selected for review. Several trials did not report CV events. Six were not randomized controlled trials (RCTs). Four studies reported no events in either intervention arm while the other four had 40 events in the febuxostat group ( n = 3631) and 5 in allopurinol group ( n = 1154). Overall, the pooled analysis did not show a significant difference between the two [febuxostat vs allopurinol: relative risk (RR) 1.69 (95% CI 0.54, 5.34), P = 0.37]. CV events did not decrease over time. Comparing shorter studies (<52 weeks) to longer ones did not reveal any statistical differences. However, in long-term studies with febuxostat vs allopurinol, results were nearly significant, with more CVE occurring with febuxostat treatment. Comparing any ULT to placebo (eight studies, n = 2221 patients) did not demonstrate a significant difference in non-Anti-Platelet Trialists' Collaboration events [any ULT vs placebo: RR 1.47 (95% CI 0.49, 4.40), P = 0.49] or all-cause mortality [any ULT vs placebo: RR 1.45 (95% CI 0.35, 5.77), P = 0.60].
Conclusion:
RCT data do not suggest differences in CV events among ULTs in gout. Trials had few events despite high-risk patients being enrolled and may have been too short to show CV reduction by controlling inflammatory attacks and lowering uric acid.