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The <jats:styled-content style=\"fixed-case\">CARES<\/jats:styled-content> trial showed no significant difference between allopurinol and febuxostat in the primary composite end point of cardiovascular (<jats:styled-content style=\"fixed-case\">CV<\/jats:styled-content>) events in subjects with gout and established <jats:styled-content style=\"fixed-case\">CV<\/jats:styled-content> comorbidities at baseline. However, there was a significantly increased risk of <jats:styled-content style=\"fixed-case\">CV<\/jats:styled-content> and all\u2010cause mortality with febuxostat. Urate\u2010lowering therapy (<jats:styled-content style=\"fixed-case\">ULT<\/jats:styled-content>) is central to the long\u2010term management of gout, and xanthine oxidoreductase inhibitor (<jats:styled-content style=\"fixed-case\">XOI<\/jats:styled-content>) therapy is the consensus first\u2010line approach. Allopurinol is generally the first <jats:styled-content style=\"fixed-case\">XOI<\/jats:styled-content> used, but febuxostat is an effective <jats:styled-content style=\"fixed-case\">XOI<\/jats:styled-content> option, and is commonly used when allopurinol is not tolerated. These data are further relevant since <jats:styled-content style=\"fixed-case\">CV<\/jats:styled-content> comorbidities are common in gout. Here, we examine why the <jats:styled-content style=\"fixed-case\">CARES<\/jats:styled-content> 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 <jats:styled-content style=\"fixed-case\">CARES<\/jats:styled-content> trial, and appraise the robustness and biologic plausibility of the results. The <jats:styled-content style=\"fixed-case\">CARES<\/jats:styled-content> trial does not prove that febuxostat raises <jats:styled-content style=\"fixed-case\">CV<\/jats:styled-content> mortality risk, but suggests greater risk with febuxostat than allopurinol. The <jats:styled-content style=\"fixed-case\">CARES<\/jats:styled-content> trial results do not support first\u2010line use of febuxostat <jats:styled-content style=\"fixed-case\">ULT<\/jats:styled-content>, and raise questions about febuxostat placement at various pharmacologic <jats:styled-content style=\"fixed-case\">ULT<\/jats:styled-content> decision tree branches. Alternatives to febuxostat that are frequently effective include allopurinol dose escalation and uricosuric therapy alone or combined with allopurinol. The <jats:styled-content style=\"fixed-case\">FDA<\/jats:styled-content> safety alert highlights the need for shared <jats:styled-content style=\"fixed-case\">ULT<\/jats:styled-content> medical decision\u2010making with gout patients, including discussion of the <jats:styled-content style=\"fixed-case\">CV<\/jats:styled-content> safety of febuxostat.<\/jats:p>","DOI":"10.1002\/art.40583","type":"journal-article","created":{"date-parts":[[2018,6,5]],"date-time":"2018-06-05T06:44:41Z","timestamp":1528181081000},"page":"1702-1709","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":102,"title":["New Perspectives in Rheumatology: Implications of the Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities Trial and the Associated Food and Drug Administration Public Safety Alert"],"prefix":"10.1002","volume":"70","author":[{"given":"Hyon","family":"Choi","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuhina","family":"Neogi","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Stamp","sequence":"additional","affiliation":[{"name":"University of Otago Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Dalbeth","sequence":"additional","affiliation":[{"name":"University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Terkeltaub","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System and University of California San Diego La Jolla California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,26]]},"reference":[{"key":"e_1_2_3_2_1","unstructured":"US Food and Drug Administration.FDA alert: febuxostat(marketed as Uloric). 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