title: As compared to allopurinol, urate-lowering therapy with febuxostat has superior effects on oxidative stress and pulse wave velocity in patients with severe chronic tophaceous gout.
abstract: We prospectively evaluated whether an effective 12-month uric acid-lowering therapy (ULT) with the available xanthine oxidase (XO) inhibitors allopurinol and febuxostat in patients with chronic tophaceous gout has an impact on oxidative stress and/or vascular function. Patients with chronic tophaceous gout who did not receive active ULT were included. After clinical evaluation, serum uric acid levels (SUA) and markers of oxidative stress were measured, and carotid-femoral pulse wave velocity (cfPWV) was assessed. Patients were then treated with allopurinol (n = 9) or with febuxostat (n = 8) to target a SUA level ≤ 360 μmol/L. After 1 year treatment, the SUA levels, markers of oxidative stress and the cfPWV were measured again. Baseline characteristics of both groups showed no significant differences except a higher prevalence of moderate impairment of renal function (estimated glomerular filtration rate <60 ml/min) in the febuxostat group. Uric acid lowering with either inhibitors of XO resulted in almost equally effective reduction in SUA levels. The both treatment groups did not differ in their baseline cfPWV (allopurinol group: 14.1 ± 3.4 m/s, febuxostat group: 13.7 ± 2.7 m/s, p = 0.80). However, after 1 year of therapy, we observed a significant cfPWV increase in the allopurinol group (16.8 ± 4.3 m/s, p = 0.001 as compared to baseline), but not in the febuxostat patients (13.3 ± 2.3 m/s, p = 0.55). Both febuxostat and allopurinol effectively lower SUA levels in patients with severe gout. However, we observed that febuxostat also appeared to be beneficial in preventing further arterial stiffening. Since cardiovascular events are an important issue in treating patients with gout, this unexpected finding may have important implications and should be further investigated in randomized controlled trials.
authors.affiliation: Department of Rheumatology, University Clinic "Carl Gustav Carus" at the Technical University Dresden, Fetscherstrasse 74, 01307, Dresden, Germany, anne-kathrin.tausche@uniklinikum-dresden.de.
authors.forename: A-K
authors.initials: AK
authors.lastname: Tausche
authors.forename: M
authors.initials: M
authors.lastname: Christoph
authors.forename: M
authors.initials: M
authors.lastname: Forkmann
authors.forename: U
authors.initials: U
authors.lastname: Richter
authors.forename: S
authors.initials: S
authors.lastname: Kopprasch
authors.forename: C
authors.initials: C
authors.lastname: Bielitz
authors.forename: M
authors.initials: M
authors.lastname: Aringer
authors.forename: C
authors.initials: C
authors.lastname: Wunderlich
mesh_terms: D000368:Aged; D000493:Allopurinol / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000069465:Febuxostat; D005858:Germany; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006073:Gout / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006074:Gout Suppressants / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D011446:Prospective Studies; D063177:Pulse Wave Analysis; D012720:Severity of Illness Index; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood*; D059289:Vascular Stiffness / Q000187:drug effects*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D006074:Gout Suppressants; D018836:Inflammation Mediators; D013844:Thiazoles; D000069465:Febuxostat; D014527:Uric Acid; D000493:Allopurinol; D014969:Xanthine Oxidase
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