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Cardiovascular risk associated with allopurinol vs. benzbromarone in patients with gout
Eun Ha Kang1, Eun Hye Park2, Anna Shin1
1Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, 166 Gumiro Bundang-gu, Seongnam, South Korea.
Insights
This study found that allopurinol increased cardiovascular risks and mortality in gout patients compared to benzbromarone. Benzbromarone may offer better cardiovascular safety for gout management.
Area of Science:
- Pharmacology
- Cardiology
- Rheumatology
Background:
- Gout is prevalent and linked to cardiovascular (CV) diseases.
- Comparative CV safety data for urate-lowering drugs, especially uricosuric agents, is limited.
- Understanding drug-specific CV risk is crucial for managing gout patients.
Purpose of the Study:
- To compare the cardiovascular risk between allopurinol and benzbromarone in gout patients.
- To investigate the CV safety profile of uricosuric agents versus a xanthine oxidase inhibitor.
- To assess the association of allopurinol and benzbromarone initiation with major adverse CV events and mortality.
Main Methods:
- A large-scale Korean National Health Insurance claims data cohort study (2002-2017).
- Included 124,434 gout patients initiating either allopurinol or benzbromarone, matched using propensity scores (5:1 ratio).
- Utilized cause-specific hazard models to estimate hazard ratios (HRs) for a composite CV endpoint (myocardial infarction, stroke/transient ischaemic attack, coronary revascularization) and all-cause mortality, accounting for competing risks.
Main Results:
- Allopurinol initiation was associated with a higher incidence of composite CV events (HR 1.22; 95% CI 1.05-1.41) compared to benzbromarone.
- The risk of all-cause mortality was also significantly higher in allopurinol initiators (HR 1.66; 95% CI 1.43-1.93).
- Mean follow-up was 1.16 years, with 2258 composite CV events observed.
Conclusions:
- In this population-based cohort, allopurinol use in gout patients was linked to increased CV events and mortality compared to benzbromarone.
- Benzbromarone may potentially offer improved CV risk reduction and mortality benefit in gout patients.
- Further research is warranted to confirm these findings and elucidate the underlying mechanisms.
Aims:
With the high prevalence of gout and associated cardiovascular (CV) diseases, information on the comparative CV safety of individual urate-lowering drugs becomes increasingly important. However, few studies examined the CV risk of uricosuric agents. We compared CV risk among patients with gout who initiated allopurinol vs. benzbromarone.
Methods And Results:
Using the Korean National Health Insurance claims data (2002-17), we conducted a cohort study of 124 434 gout patients who initiated either allopurinol (n = 103 695) or benzbromarone (n = 20 739), matched on propensity score at a 5:1 ratio. The primary outcome was a composite CV endpoint of myocardial infarction, stroke/transient ischaemic attack, or coronary revascularization. To account for competing risk of death, we used cause-specific hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the outcomes comparing allopurinol initiators with benzbromarone. Over a mean follow-up of 1.16 years, 2258 patients developed a composite CV event. The incidence rate of the composite CV event was higher in allopurinol initiators (1.81 per 100 person-years) than benzbromarone (1.61 per 100 person-years) with a HR of 1.22 (95% CI 1.05-1.41). The HR for all-cause mortality was 1.66 (95% CI 1.43-1.93) among allopurinol initiators compared with benzbromarone.
Conclusion:
In this large population-based cohort of gout patients, allopurinol was associated with an increased risk of composite CV events and all-cause mortality compared to benzbromarone. Benzbromarone may reduce CV risk and mortality in patients with gout, although more studies are necessary to confirm our findings and to advance our understanding of the underlying mechanisms.
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