Journal article
Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout
The New England journal of medicine, Vol.378(13), pp.1200-1210
03/29/2018
DOI: 10.1056/NEJMoa1710895
PMID: 29527974
Abstract
Cardiovascular risk is increased in patients with gout. We compared cardiovascular outcomes associated with febuxostat, a nonpurine xanthine oxidase inhibitor, with those associated with allopurinol, a purine base analogue xanthine oxidase inhibitor, in patients with gout and cardiovascular disease.
We conducted a multicenter, double-blind, noninferiority trial involving patients with gout and cardiovascular disease; patients were randomly assigned to receive febuxostat or allopurinol and were stratified according to kidney function. The trial had a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point (a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina with urgent revascularization).
In total, 6190 patients underwent randomization, received febuxostat or allopurinol, and were followed for a median of 32 months (maximum, 85 months). The trial regimen was discontinued in 56.6% of patients, and 45.0% discontinued follow-up. In the modified intention-to-treat analysis, a primary end-point event occurred in 335 patients (10.8%) in the febuxostat group and in 321 patients (10.4%) in the allopurinol group (hazard ratio, 1.03; upper limit of the one-sided 98.5% confidence interval [CI], 1.23; P=0.002 for noninferiority). All-cause and cardiovascular mortality were higher in the febuxostat group than in the allopurinol group (hazard ratio for death from any cause, 1.22 [95% CI, 1.01 to 1.47]; hazard ratio for cardiovascular death, 1.34 [95% CI, 1.03 to 1.73]). The results with regard to the primary end point and all-cause and cardiovascular mortality in the analysis of events that occurred while patients were being treated were similar to the results in the modified intention-to-treat analysis.
In patients with gout and major cardiovascular coexisting conditions, febuxostat was noninferior to allopurinol with respect to rates of adverse cardiovascular events. All-cause mortality and cardiovascular mortality were higher with febuxostat than with allopurinol. (Funded by Takeda Development Center Americas; CARES ClinicalTrials.gov number, NCT01101035 .).
Details
- Title: Subtitle
- Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout
- Creators
- William B White - From the University of Connecticut School of Medicine, Farmington (W.B.W.); the University of Alabama, Birmingham (K.G.S.); University of Chicago Medicine, Chicago (M.A.B.), and Takeda Development Center Americas, Deerfield (B.H., M.C., L.G.) - both in Illinois; the State University of New York, Downstate Medical Center, Brooklyn (J.S.B.); Michigan State University College of Human Medicine, Grand Rapids (P.B.G.); and Johns Hopkins University School of Medicine, Baltimore (A.W.)Kenneth G Saag - University of Alabama at BirminghamMichael A Becker - From the University of Connecticut School of Medicine, Farmington (W.B.W.); the University of Alabama, Birmingham (K.G.S.); University of Chicago Medicine, Chicago (M.A.B.), and Takeda Development Center Americas, Deerfield (B.H., M.C., L.G.) - both in Illinois; the State University of New York, Downstate Medical Center, Brooklyn (J.S.B.); Michigan State University College of Human Medicine, Grand Rapids (P.B.G.); and Johns Hopkins University School of Medicine, Baltimore (A.W.)Jeffrey S Borer - From the University of Connecticut School of Medicine, Farmington (W.B.W.); the University of Alabama, Birmingham (K.G.S.); University of Chicago Medicine, Chicago (M.A.B.), and Takeda Development Center Americas, Deerfield (B.H., M.C., L.G.) - both in Illinois; the State University of New York, Downstate Medical Center, Brooklyn (J.S.B.); Michigan State University College of Human Medicine, Grand Rapids (P.B.G.); and Johns Hopkins University School of Medicine, Baltimore (A.W.)Philip B Gorelick - From the University of Connecticut School of Medicine, Farmington (W.B.W.); the University of Alabama, Birmingham (K.G.S.); University of Chicago Medicine, Chicago (M.A.B.), and Takeda Development Center Americas, Deerfield (B.H., M.C., L.G.) - both in Illinois; the State University of New York, Downstate Medical Center, Brooklyn (J.S.B.); Michigan State University College of Human Medicine, Grand Rapids (P.B.G.); and Johns Hopkins University School of Medicine, Baltimore (A.W.)Andrew Whelton - From the University of Connecticut School of Medicine, Farmington (W.B.W.); the University of Alabama, Birmingham (K.G.S.); University of Chicago Medicine, Chicago (M.A.B.), and Takeda Development Center Americas, Deerfield (B.H., M.C., L.G.) - both in Illinois; the State University of New York, Downstate Medical Center, Brooklyn (J.S.B.); Michigan State University College of Human Medicine, Grand Rapids (P.B.G.); and Johns Hopkins University School of Medicine, Baltimore (A.W.)Barbara Hunt - From the University of Connecticut School of Medicine, Farmington (W.B.W.); the University of Alabama, Birmingham (K.G.S.); University of Chicago Medicine, Chicago (M.A.B.), and Takeda Development Center Americas, Deerfield (B.H., M.C., L.G.) - both in Illinois; the State University of New York, Downstate Medical Center, Brooklyn (J.S.B.); Michigan State University College of Human Medicine, Grand Rapids (P.B.G.); and Johns Hopkins University School of Medicine, Baltimore (A.W.)Majin Castillo - From the University of Connecticut School of Medicine, Farmington (W.B.W.); the University of Alabama, Birmingham (K.G.S.); University of Chicago Medicine, Chicago (M.A.B.), and Takeda Development Center Americas, Deerfield (B.H., M.C., L.G.) - both in Illinois; the State University of New York, Downstate Medical Center, Brooklyn (J.S.B.); Michigan State University College of Human Medicine, Grand Rapids (P.B.G.); and Johns Hopkins University School of Medicine, Baltimore (A.W.)Lhanoo Gunawardhana - From the University of Connecticut School of Medicine, Farmington (W.B.W.); the University of Alabama, Birmingham (K.G.S.); University of Chicago Medicine, Chicago (M.A.B.), and Takeda Development Center Americas, Deerfield (B.H., M.C., L.G.) - both in Illinois; the State University of New York, Downstate Medical Center, Brooklyn (J.S.B.); Michigan State University College of Human Medicine, Grand Rapids (P.B.G.); and Johns Hopkins University School of Medicine, Baltimore (A.W.)CARES Investigators
- Contributors
- Craig T Morita (Contributor) - University of Iowa, Immunology
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.378(13), pp.1200-1210
- DOI
- 10.1056/NEJMoa1710895
- PMID
- 29527974
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Grant note
- DOI: 10.13039/100007723, name: Takeda Pharmaceuticals U.S.A.
- Language
- English
- Date published
- 03/29/2018
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984094378702771
Metrics
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