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Allopurinol therapy in gout patients does not associate with beneficial cardiovascular outcomes: a population-based
Victor C Kok1, Jorng-Tzong Horng2, Wan-Shan Chang3
1Public Health and Clinical Informatics Research Group, Department of Biomedical Informatics, Asia University, Wufeng, Taichung, Taiwan; Department of Internal Medicine, Kuang Tien General Hospital, Shalu, Taichung, Taiwan.
Insights
Allopurinol therapy in gout patients did not show beneficial cardiovascular outcomes. Uricosuric agents, however, were associated with reduced cardiovascular events compared to allopurinol.
Area of Science:
- Rheumatology
- Cardiology
- Pharmacology
Background:
- Gout and hyperuricemia are linked to increased cardiovascular disease (CVD) risk.
- Allopurinol is known to reduce oxidative stress and inflammation, potentially benefiting vascular health.
Purpose of the Study:
- To investigate the association between allopurinol therapy and future cardiovascular outcomes in gout patients.
- To compare cardiovascular event rates between allopurinol users and non-users.
Main Methods:
- A population-based matched-cohort study design was employed.
- 2483 gout patients receiving allopurinol were matched with 2483 non-users based on key demographic and clinical factors.
- Follow-up occurred for a median of 5.25 years.
Main Results:
- The allopurinol group showed a modest increase in cardiovascular risk (RR 1.20, 95% CI 1.08-1.34).
- Adjusted analysis revealed a hazard ratio of 1.25 (95% CI 1.10-1.41) for cardiovascular outcomes in allopurinol users.
- Uricosuric agent users (n=1713) had a significantly lower adjusted HR of 0.83 (0.73-0.95) for cardiovascular events compared to allopurinol users.
Conclusions:
- This study did not support a beneficial association between allopurinol and future cardiovascular outcomes in gout patients.
- Limitations include the inability to account for crucial risk factors like smoking and BMI, potentially biasing results.
- Uricosuric agents may offer a more favorable cardiovascular profile in gout management.
Introduction:
Previous studies have shown an association between gout and/or hyperuricemia and a subsequent increase in cardiovascular disease (CVD) outcomes. Allopurinol reduces vascular oxidative stress, ameliorates inflammatory state, improves endothelial function, and prevents atherosclerosis progression. Accordingly, we tested the hypothesis that a positive association between allopurinol therapy in gout patients and future cardiovascular outcomes is present using a population-based matched-cohort study design.
Methods:
Patients aged ≥40 years with newly diagnosed gout having no pre-existing severe form of CVD were separated into allopurinol (n = 2483) and non-allopurinol (n = 2483) groups after matching for age, gender, index date, diabetes mellitus, hypertension, hyperlipidemia, and atrial fibrillation. The two groups were also balanced in terms of uric acid nephrolithiasis, acute kidney injury, hepatitis, and Charlson comorbidity index.
Results:
With a median follow-up time of 5.25 years, the allopurinol group had a modest increase in cardiovascular risk [relative risk, 1.20; 95% confidence interval (CI), 1.08-1.34]. A Cox proportional hazard model adjusted for chronic kidney disease, uremia, and gastric ulcer gave a hazard ratio (HR) for cardiovascular outcomes of 1.25 (95% CI, 1.10-1.41) in gout patients receiving allopurinol compared with the non-allopurinol group. In further analysis of patients receiving urate-lowering therapy, the uricosuric agent group (n = 1713) had an adjusted HR of 0.83 (0.73-0.95) for cardiovascular events compared with the allopurinol group.
Conclusions:
The current population-based matched-cohort study did not support the association between allopurinol therapy in gout patients with normal risk for cardiovascular sequels and beneficial future cardiovascular outcomes. Several important risk factors for cardiovascular disease, such as smoking, alcohol consumption, body mass index, blood pressure were not obtainable in the current retrospective cohort study, thus could potentially bias the effect estimate.