Cardiovascular Safety of Febuxostat Versus Allopurinol in the Real World: Old Reliable Comes Out on Top

Mankad, Rekha

doi:10.1016/j.mayocp.2019.05.012

Cited by 3 publications

(1 citation statement)

References 15 publications

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“…Febuxostat was usually reimbursed when allopurinol or uricosuric treatment was ineffective in achieving target uric acid levels and in individuals who were intolerant to allopurinol. Gout patients who were resistant or intolerant to allopurinol or uricosuric treatment might be at higher risk of hyperuricemia than those who achieved effective control with allopurinol alone ( 44 ). Thus, we used a new-users design to minimize this confounding bias, as patients did not receive any study drug before 1 year on the index date.…”

Section: Discussionmentioning

confidence: 99%

Sex difference in heart failure risk associated with febuxostat and allopurinol in gout patients

Cheng

Yen²,

Su³

et al. 2022

Front. Cardiovasc. Med.

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BackgroundGout or rapid reduction in serum uric acid level may increase the incidence of heart failure (HF). To compare the risk of HF between febuxostat and allopurinol in gout patients with coexisting cardiovascular (CV) diseases, the varying severity would be likely to confound the risk estimation. Gout and HF are both sex-related diseases, and the risk difference from the urate-lowering agents between women and men remains unknown.AimsTo evaluate the HF hospitalisations risk of febuxostat and allopurinol in gout patients in real-world settings.MethodsA population-based cohort enrolled patients with allopurinol or febuxostat initiation from 2011 to 2018. Participants were grouped into, without (low CV risk group) or with (high CV risk group) a history of recent major CV admission. The primary outcome was HF hospitalization. The secondary outcomes were composite CV events, all-cause mortality, and the cause of CV mortality. We used the ‘as-treated' analysis and Cox proportional hazards model after propensity score (PS) matching. Patients were further stratified into men and women to evaluate the gender differences.ResultsFebuxostat users had a significantly higher risk of HF hospitalization than allopurinol users in gout patients either with low CV risk [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.25–1.55] or high CV risk [HR 1.36; 95% CI 1.22–1.52]. Particularly, women with gout had a higher risk of HF hospitalization than men.ConclusionThe HF hospitalization risk was highest in gout women with high CV risk and febuxostat use. Monitoring of HF is warranted in these patients.

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Section: Discussionmentioning

confidence: 99%

Sex difference in heart failure risk associated with febuxostat and allopurinol in gout patients

Cheng

Yen²,

Su³

et al. 2022

Front. Cardiovasc. Med.

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Febuxostat vs allopurinol: real-world cardiovascular safety

2019

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Xanthine oxidase inhibitor febuxostat reduces atrial fibrillation susceptibility by inhibition of oxidized CaMKII in Dahl salt-sensitive rats

Murakoshi

Tajiri

et al. 2021

Clinical Science

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Oxidative stress could be a possible mechanism and a therapeutic target of atrial fibrillation (AF). However, the effects of the xanthine oxidase (XO) inhibition for AF remain to be fully elucidated. We investigated the effects of a novel XO inhibitor febuxostat on AF compared to allopurinol in hypertension rat model. Five-week-old Dahl salt-sensitive rats were fed to either low-salt (LS) (0.3% NaCl) or high-salt (HS) (8% NaCl) diet. After 4 weeks of diet, HS diet rats were divided into 3 groups: orally administered to vehicle (HS-C), febuxostat (5mg/kg/day) (HS-F), or allopurinol (50mg/kg/day) (HS-A). After 4 weeks of treatment, systolic blood pressure was significantly higher in HS-C than LS, and it was slightly but significantly decreased by treatment with each XO inhibitor. AF duration was significantly prolonged in HS-C compared with LS, and significantly suppressed in both HS-F and HS-A (LS; 5.8±3.5 sec, HS-C; 33.9±23.7 sec, HS-F; 15.0±14.1 sec, HS-A; 20.1±11.9 sec: P<0.05). Ca2+ spark frequency was obviously increased in HS-C rats and reduced in the XO inhibitor-treated rats, especially in HS-F group. Western blotting revealed that the atrial expression levels of methionine 281/282-oxidized Ca2+/Calmodulin-dependent kinase II and serine 2814-phosphorylated ryanodine receptor 2 were significantly increased in HS-C, and those were suppressed in HS-F and HS-A. Decreased expression of gap junction protein connexin 40 in HS-C was partially restored by treatment with each XO inhibitor. In conclusion, XO inhibitor febuxostat, as well as allopurinol, could reduce hypertension-related increase in AF perpetuation by restoring Ca2+ handling and gap junction.

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Cardiovascular Safety of Febuxostat Versus Allopurinol in the Real World: Old Reliable Comes Out on Top

Cited by 3 publications

References 15 publications

Sex difference in heart failure risk associated with febuxostat and allopurinol in gout patients

Sex difference in heart failure risk associated with febuxostat and allopurinol in gout patients

Febuxostat vs allopurinol: real-world cardiovascular safety

Xanthine oxidase inhibitor febuxostat reduces atrial fibrillation susceptibility by inhibition of oxidized CaMKII in Dahl salt-sensitive rats

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