All-cause mortality lower with use of allopurinol, febuxostat for adults on hemodialysis
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Key takeaways:
- Risk of death from all causes was similarly lower for patients on hemodialysis prescribed either allopurinol or febuxostat.
- Risk of CVD-related death was lower for those on allopurinol, but not febuxostat.
Allopurinol and febuxostat were both associated with lower all-cause mortality when used by adults undergoing hemodialysis in Japan; allopurinol also lowered risk of death from CVD events, according to study data.
Allopurinol and febuxostat (Uloric, Takeda) are xanthine oxidoreductase inhibitors used to reduce uric acid levels. Previous studies have shown increased risks for all-cause and CVD mortality with febuxostat use compared with allopurinol in the treatment of gout, according to study background.
“This is the first study to evaluate the respective effects of allopurinol and febuxostat compared with those of non-treatment on cardiovascular outcomes in patients receiving hemodialysis, particularly in those with deteriorated kidney function and residual intestine excretion channels,” Takeo Ishii MD, PhD, of the department of medical science and cardiorenal medicine at Yokohama City University Graduate School of Medicine and Yokohama Daiichi Hospital Zenjinkai in Japan, and colleagues wrote in Kidney Medicine.
The researchers analyzed medical records data from 6,791 adults who underwent hemodialysis in Japan from April 2016 to March 2019. Participants had not used topiroxostat, a xanthine oxidoreductase inhibitor used in Japan to treat gout.
At baseline, 775 participants had a prescription for allopurinol, 860 had a prescription for febuxostat and 5,156 participants had a no prescription and were considered not treated.
In marginal structural Cox hazard models, all-cause mortality risks were significantly lower for the allopurinol (HR = 0.4; 95% CI, 0.3-0.54) and febuxostat (HR = 0.49; 95% CI, 0.36-0.63) groups compared with the non-treatment group and similar between treatment groups.
Researchers used two models to account for recurrent CVD events: the Andersen and Gill (AG) and the Prentice, Williams and Peterson (PWP).
Risk of CVD mortality was significantly lower compared with non-treatment for allopurinol (AG model HR = 0.85; 95% CI, 0.8-0.91 and the PWP model HR = 0.89; 95% CI, 0.84-0.95), but not for febuxostat, and was also lower for allopurinol vs. febuxostat (AG model HR = 0.84; 95% CI, 0.78-0.91 and PWP model HR = 0.88; 95% CI, 0.82-0.95).
Risk of death from heart failure was lower compared with non-treatment for allopurinol (AG model HR = 0.69; 95% CI, 0.54-0.88 and the PWP model HR = 0.71; 95% CI, 0.56-0.9), but not febuxostat, and for allopurinol vs. febuxostat (AG model HR = 0.68; 95% CI, 0.56-0.84 and PWP model HR = 0.73; 95% CI, 0.6-0.89).
Similarly, risk of death from acute myocardial infarction was lower compared with non-treatment for allopurinol (AG model HR = 0.45; 95% CI, 0.23-0.85 and the PWP model HR = 0.48; 95% CI, 0.25-0.91), but not for febuxostat.
“[In this study], allopurinol and febuxostat had stronger xanthine oxidoreductase inhibitory effects than non-treatment. However, febuxostat was not inferior to allopurinol in terms of all-cause mortality,” the researchers wrote. “The involvement of ABCG2 is considered a possibility, although conclusive evidence is yet to be established. Therefore, further investigations that do not affect gut excretion should be conducted.”
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