非布索坦
别嘌呤醇
医学
痛风
药理学
黄嘌呤氧化酶抑制剂
高尿酸血症
内科学
尿酸
黄嘌呤氧化酶
化学
生物化学
酶
作者
Hyon K. Choi,Tuhina Neogi,Lisa K. Stamp,Nicola Dalbeth,Robert Terkeltaub
摘要
Recently, the US Food and Drug Administration ( FDA ) issued a public safety alert, responding to the results of the now‐published Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities ( CARES ) trial. The CARES trial showed no significant difference between allopurinol and febuxostat in the primary composite end point of cardiovascular ( CV ) events in subjects with gout and established CV comorbidities at baseline. However, there was a significantly increased risk of CV and all‐cause mortality with febuxostat. Urate‐lowering therapy ( ULT ) is central to the long‐term management of gout, and xanthine oxidoreductase inhibitor ( XOI ) therapy is the consensus first‐line approach. Allopurinol is generally the first XOI used, but febuxostat is an effective XOI option, and is commonly used when allopurinol is not tolerated. These data are further relevant since CV comorbidities are common in gout. Here, we examine why the CARES trial was done, and discuss other, ongoing comparative studies of febuxostat and allopurinol whose results are awaited. We assess the strengths and limitations of the CARES trial, and appraise the robustness and biologic plausibility of the results. The CARES trial does not prove that febuxostat raises CV mortality risk, but suggests greater risk with febuxostat than allopurinol. The CARES trial results do not support first‐line use of febuxostat ULT , and raise questions about febuxostat placement at various pharmacologic ULT decision tree branches. Alternatives to febuxostat that are frequently effective include allopurinol dose escalation and uricosuric therapy alone or combined with allopurinol. The FDA safety alert highlights the need for shared ULT medical decision‐making with gout patients, including discussion of the CV safety of febuxostat.
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