Excess Deaths Upon Cessation of Xanthine Oxidase Inhibitor Treatment—Data From the Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities Trial: Comment on the Article by Choi et al

Xanthine Oxidase Inhibitor Withdrawal Syndrome? Comment on the Article by Choi et al

“…The primary, key secondary, secondary, and additional end points all had a significant component of subjective assessment by both patient-reported measures (e.g., patient global assessment, patient pain assessment, Health Assessment Questionnaire) and physician-reported measures. Although we do not dispute the importance of patient-reported measures, it should be noted that these assessments can be affected by factors independent of active synovitis in patients with PsA (2). Indeed, active enthesitis and axial disease, which often accompany PsA (and may be less affected by methotrexate) (3), may continue to drive higher composite scores by contributing to patient pain and patient global assessment of disease despite improvement in joint counts.…”

Uric Acid as a Risk Factor for Chronic Kidney Disease and Cardiovascular Disease ― Japanese Guideline on the Management of Asymptomatic Hyperuricemia ―

“…Although the key issue in the CARES study 71 was the higher CVD death rates and all-causes mortality in Americans treated with febuxostat vs. allopurinol, the data that attracted attention was a drastic increase in major adverse CVD events after quitting these drugs when subjects went "off-drug". 75,76 It has been reported that the mean percentage of CV death in patients was 0.17% and 0.085% per month for 4 years with febuxostat and allopurinol, respectively. 76 This rate increased to 2.19% and 1.56% per month, respectively, during the first 30 off-drug days.…”

Association of Mutations Identified in Xanthinuria with the Function and Inhibition Mechanism of Xanthine Oxidoreductase

“…On the other hand, it has been suggested that inhibition of XOR may have reduced cardiovascular damage and death. In the CARES trial, more than half of the patients stopped taking their medication, and a detailed study including these dropouts showed that the majority of deaths occurred in the absence of medication [ 40 , 41 , 42 ]. There have been many reports that XOR inhibitors ameliorate cardiovascular disorders, especially based on the association with oxidative stress [ 43 , 44 , 45 , 46 ].…”