Comparison of Febuxostat and Allopurinol for Hyperuricemia in Cardiac Surgery Patients (NU-FLASH Trial)

Sezai, Akira; Soma, Masayoshi; Nakata, Kohei; Hata, Mitsumasa; Yoshitake, Isamu; Wakui, Shinji; Hata, Hiroyuki; Shiono, Motomi

doi:10.1253/circj.cj-13-0082

Cited by 103 publications

(102 citation statements)

References 25 publications

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“…Several recent studies have been investigating therapeutic interventions to delay nephropathy progression [63][64][65] . Allopurinol therapy significantly decreases SUA levels in hyperuricemic patients with mild to moderate CKD.…”

Section: Atherosclerosis and Xdh/xo In Monocytes/macrophagesmentioning

confidence: 99%

“…Its use is safe and has been shown to help preserve kidney function when used for a duration of 12 mo [63] . Febuxostat has a higher renoprotective effect than allopurinol, inhibits oxidative stress, has anti-atherogenic activity, reduces blood pressure, and decreases pulse wave velocity and left ventricular mass index, most likely due to a strong SUA lowering effect [65] . In an animal diabetic nephropathy model, allopurinol attenuated transforming growth factor-beta1-induced Smad pathway activation in tubular cells [66] .…”

Section: Atherosclerosis and Xdh/xo In Monocytes/macrophagesmentioning

confidence: 99%

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Linking uric acid metabolism to diabetic complications

Kushiyama

Tanaka

Hara

et al. 2014

WJD

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Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase (XDH/ XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid (UA) generation inhibitor in the 1950s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target for vascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Uric acid; Xanthine dehydrogenase/xanthine oxidase; Diabetes mellitus; Diabetic complications; Xanthine oxidase inhibitor; Metabolism Core tip: Uric acid (UA) is derived from essential metabolism, and UA metabolism is becoming a novel risk and interventional factor of lifestyle-related diseases in this obesity-prone era. The relationship between UA metabolism and diabetic complications is highlighted in this review and supposed molecular mechanisms are mentioned.Kushiyama A, Tanaka K, Hara S, Kawazu S. Linking uric acid metabolism to diabetic complications. World J Diabetes 2014; 5(6): 787-795 Available from:

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Section: Atherosclerosis and Xdh/xo In Monocytes/macrophagesmentioning

confidence: 99%

Section: Atherosclerosis and Xdh/xo In Monocytes/macrophagesmentioning

confidence: 99%

Linking uric acid metabolism to diabetic complications

Kushiyama

Tanaka

Hara

et al. 2014

WJD

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“…95 Data from experimental and clinical studies reported that lowering UA by using XO inhibitors may lead to a decrease in DOI: 10.3109/0886022X.2014.947516 blood pressure, supporting a direct effect of UA. 8,[96][97][98] However, Gois and Souza 99 reported that there is insufficient evidence of an antihypertensive effect of allopurinol.…”

Section: Hua Hypertension and Ckdmentioning

confidence: 99%

Hyperuricemia and chronic kidney disease: an enigma yet to be solved

et al. 2014

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The role of uric acid (UA) on the pathogenesis and progression of chronic kidney disease (CKD) remains controversial. Experimental and clinical studies indicate that UA is associated with several risk factors of CKD including diabetes, hypertension, oxidative stress, and inflammation and hyperuricemia could be considered as a common dominator linking CKD and cardiovascular disease. Notably, the impact of serum UA levels on the survival of CKD, dialysis patients, and renal transplant recipients is also a matter of debate, as there are conflicting results from clinical studies. At present, there is no definite data whether UA is causal, compensatory, coincidental or it is only an epiphenomenon in these patients. In this article, we attempt to review and elucidate the dark side of this old molecule in CKD and renal transplantation.

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“…The dose was increased up to a maximum of 60 mg/day for febuxostat or 160 mg/day for topiroxostat. Exclusion criteria were (1) renal dysfunction with an estimated glomerular filtration rate (eGFR) ≤20 mL/min/1.73 m 2 ; (2) hepatic dysfunction (aspartate aminotransferase [AST] >39 U/L or alanine aminotransferase [ALT] >44 U/L); (3) treatment with mercaptopurine hydrate or azathiopurine; (4) pregnancy; (5) other reasons that made patients unsuitable for this study as judged by the attending physician. This study was conducted at Sekino Hospital, a logistical support hospital of Nihon University Itabashi Hospital.…”

mentioning

confidence: 99%

Cross-Over Trial of Febuxostat and Topiroxostat for Hyperuricemia With Cardiovascular Disease (TROFEO Trial)

Sezai

Obata²,

Abé³

et al. 2017

Circ J

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to reduce UA more potently than allopurinol, 7 while topiroxostat has a similar effect to allopurinol. 8 No study, however, has compared febuxostat with topiroxostat. Accordingly, a clinical study was conducted to compare febuxostat with topiroxostat and assess potential differences in efficacy (TopiROxostat and FEbuxostat in a randomized, Open-label, cross-over trial for hyperuricemia with cardiovascular disease (TROFEO trial). Methods Study ProtocolThe subjects were outpatients with cardiovascular disease and hyperuricemia in whom s-UA was controlled at ≤6 mg/dL by treatment with allopurinol or febuxostat. In this study, patients were randomized by the envelop method to receive treatment with either febuxostat (Teijin Pharma, Tokyo, Japan) or topiroxostat (Sanwa Kagaku Kenkyusho, Aichi, Japan and Fujiyakuhin, Saitama, Japan) for 6 months, after which they switched to the other medication for another 6 months. Baseline data were H yperuricemia was recently reported to be associated with hypertension, cardiovascular disease, and chronic kidney disease (CKD). 1,2 Allopurinol has long been regarded as a first-line drug for the treatment of hyperuricemia, but adverse reactions such as renal dysfunction, Stevens-Johnson syndrome, and hypersensitivity vasculitis have been reported with allopurinol, and it is not sufficiently effective in some cases. 3,4 In a comparative trial of febuxostat vs. allopurinol, we reported that febuxostat reduced serum uric acid (s-UA) earlier than allopurinol, had a stronger renoprotective effect than allopurinol, and also had superior antioxidant and anti-inflammatory effects. 5,6 Unlike allopurinol, febuxostat and topiroxostat (a novel xanthine oxidase reductase [XOR] inhibitor) have a non-purine structure and are mainly metabolized in the liver. In addition, these agents are excreted in both the urine and feces. Accordingly, their impact on the kidney is minimal, and dose adjustment depending on renal function is not required, in contrast to allopurinol. These 2 drugs have different dosing regimens (once daily for febuxostat vs. twice daily for topiroxostat) and febuxostat is reported Background: We previously reported that febuxostat was more effective for hyperuricemia than allopurinol. The efficacy, however, of topiroxostat (a novel xanthine oxidase reductase inhibitor similar to febuxostat), for hyperuricemia is unknown. Methods and Results:Patients with cardiovascular disease and hyperuricemia, in whom serum uric acid (s-UA) was controlled at ≤6 mg/dL, were eligible for enrollment. Fifty-five patients were randomized to receive either febuxostat or topiroxostat for 6 months and were switched to the other drug for the following 6 months. The primary endpoint was s-UA. Secondary endpoints included serum creatinine, estimated glomerular filtration rate, urinary albumin, cystatin-C, oxidized low-density lipoprotein, eicosapentaenoic acid/ arachidonic acid ratio, lipid biomarkers, high-sensitivity C-reactive protein and B-type natriuretic protein. Although s-UA level was similar for b...

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Comparison of Febuxostat and Allopurinol for Hyperuricemia in Cardiac Surgery Patients (NU-FLASH Trial)

Cited by 103 publications

References 25 publications

Linking uric acid metabolism to diabetic complications

Linking uric acid metabolism to diabetic complications

Hyperuricemia and chronic kidney disease: an enigma yet to be solved

Cross-Over Trial of Febuxostat and Topiroxostat for Hyperuricemia With Cardiovascular Disease (TROFEO Trial)

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