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Allopurinol Versus Febuxostat Use and the Risk of Cardiovascular Disease in People With Chronic Kidney Disease: A
Reiko Inoue1, Satoko Yamaguchi1, Akira Okada1
1Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Insights
For chronic kidney disease patients, febuxostat and allopurinol showed similar cardiovascular event risks. This study compared cardiovascular outcomes for these common uric acid-lowering treatments in kidney disease populations.
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Hyperuricemia is a common comorbidity in chronic kidney disease (CKD).
- Allopurinol and febuxostat are standard treatments for hyperuricemia.
- Cardiovascular outcomes associated with these treatments in CKD patients are debated.
Purpose of the Study:
- To evaluate the risk of cardiovascular events in CKD patients treated with allopurinol versus febuxostat.
- To compare the safety profiles of febuxostat and allopurinol regarding cardiovascular health in CKD.
Main Methods:
- A new-user active comparator cohort study was conducted using Japanese insurance claims data.
- Included were individuals with estimated glomerular filtration rate < 60 mL/min/1.73 m² newly prescribed allopurinol or febuxostat.
- Primary outcome: composite of cardiovascular events (myocardial infarction, stroke, all-cause death). Multivariate and IPTW Cox regression models were used.
Main Results:
- 1673 patients received allopurinol, and 7805 received febuxostat.
- Febuxostat group showed a similar incidence of composite cardiovascular events compared to the allopurinol group (HR 0.93; 95% CI: 0.79-1.08).
- Sensitivity analysis confirmed these findings across different CKD severity levels.
Conclusions:
- No statistically significant difference in cardiovascular event risk was found between febuxostat and allopurinol in CKD patients.
- Febuxostat appears to be a safe alternative to allopurinol concerning cardiovascular outcomes in this population.
Aim:
Hyperuricaemia, a common comorbidity among people with chronic kidney disease, is widely treated with uric acid-lowering agents such as allopurinol and febuxostat. Cardiovascular outcomes of people with chronic kidney disease receiving allopurinol or febuxostat have been controversial. The present study evaluated the risk of cardiovascular events associated with allopurinol or febuxostat treatment in people with chronic kidney disease.
Methods:
We conducted a new-user active comparator cohort study using a nationwide insurance claims database in Japan. Individuals with an estimated glomerular filtration rate < 60 mL/min/1.73 m2 who were newly prescribed allopurinol or febuxostat were included. The primary outcome was a composite of cardiovascular events, including fatal and non-fatal acute myocardial infarction, fatal and non-fatal stroke, and all-cause death. Hazard ratios were estimated using a multivariate Cox regression model. A sensitivity analysis was performed using an inverse probability of treatment weighting (IPTW) Cox regression model.
Results:
A total of 1673 and 7805 individuals were included in the allopurinol and febuxostat treatment groups, respectively. The febuxostat group had a similar incidence of the composite outcome as the allopurinol group (hazard ratio 0.93, 95% confidence interval: 0.79-1.08, p = 0.33). The hazard ratio for febuxostat compared with allopurinol treatment did not vary across different estimated glomerular filtration rate levels. The sensitivity analysis using IPTW showed similar results.
Conclusion:
In conclusion, no statistically significant difference in the risk of cardiovascular events was observed in people with chronic kidney disease who were newly prescribed febuxostat compared with those newly treated with allopurinol.
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