dc.contributor.author |
Choi, Hyon |
en |
dc.contributor.author |
Neogi, Tuhina |
en |
dc.contributor.author |
Stamp, Lisa |
en |
dc.contributor.author |
Dalbeth, Nicola |
en |
dc.contributor.author |
Terkeltaub, Robert |
en |
dc.date.accessioned |
2019-03-27T21:08:55Z |
en |
dc.date.issued |
2018-11 |
en |
dc.identifier.issn |
2326-5191 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/46296 |
en |
dc.description.abstract |
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. |
en |
dc.format.medium |
Print |
en |
dc.language |
eng |
en |
dc.relation.ispartofseries |
Arthritis & rheumatology (Hoboken, N.J.) |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
Humans |
en |
dc.subject |
Gout |
en |
dc.subject |
Cardiovascular Diseases |
en |
dc.subject |
Hyperuricemia |
en |
dc.subject |
Allopurinol |
en |
dc.subject |
Xanthine Oxidase |
en |
dc.subject |
Gout Suppressants |
en |
dc.subject |
Enzyme Inhibitors |
en |
dc.subject |
Mortality |
en |
dc.subject |
Comorbidity |
en |
dc.subject |
United States Food and Drug Administration |
en |
dc.subject |
United States |
en |
dc.subject |
Japan |
en |
dc.subject |
Europe |
en |
dc.subject |
Randomized Controlled Trials as Topic |
en |
dc.subject |
Febuxostat |
en |
dc.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. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1002/art.40583 |
en |
pubs.issue |
11 |
en |
pubs.begin-page |
1702 |
en |
pubs.volume |
70 |
en |
dc.rights.holder |
Copyright: The author |
en |
pubs.end-page |
1709 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Research Support, Non-U.S. Gov't |
en |
pubs.subtype |
research-article |
en |
pubs.subtype |
Research Support, U.S. Gov't, Non-P.H.S. |
en |
pubs.subtype |
Journal Article |
en |
pubs.subtype |
Research Support, N.I.H., Extramural |
en |
pubs.elements-id |
755875 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
School of Medicine |
en |
pubs.org-id |
Medicine Department |
en |
dc.identifier.eissn |
2326-5205 |
en |
pubs.record-created-at-source-date |
2018-06-06 |
en |
pubs.dimensions-id |
29869840 |
en |