Video: Every Case Tells a Story| Webinar: ACR/CHEST ILD Guidelines in Practice

An official publication of the ACR and the ARP serving rheumatologists and rheumatology professionals

  • Conditions
    • Axial Spondyloarthritis
    • Gout and Crystalline Arthritis
    • Myositis
    • Osteoarthritis and Bone Disorders
    • Pain Syndromes
    • Pediatric Conditions
    • Psoriatic Arthritis
    • Rheumatoid Arthritis
    • Sjögren’s Disease
    • Systemic Lupus Erythematosus
    • Systemic Sclerosis
    • Vasculitis
    • Other Rheumatic Conditions
  • FocusRheum
    • ANCA-Associated Vasculitis
    • Axial Spondyloarthritis
    • Gout
    • Psoriatic Arthritis
    • Rheumatoid Arthritis
    • Systemic Lupus Erythematosus
  • Guidance
    • Clinical Criteria/Guidelines
    • Ethics
    • Legal Updates
    • Legislation & Advocacy
    • Meeting Reports
      • ACR Convergence
      • Other ACR meetings
      • EULAR/Other
    • Research Rheum
  • Drug Updates
    • Analgesics
    • Biologics/DMARDs
  • Practice Support
    • Billing/Coding
    • EMRs
    • Facility
    • Insurance
    • QA/QI
    • Technology
    • Workforce
  • Opinion
    • Patient Perspective
    • Profiles
    • Rheuminations
      • Video
    • Speak Out Rheum
  • Career
    • ACR ExamRheum
    • Awards
    • Career Development
  • ACR
    • ACR Home
    • ACR Convergence
    • ACR Guidelines
    • Journals
      • ACR Open Rheumatology
      • Arthritis & Rheumatology
      • Arthritis Care & Research
    • From the College
    • Events/CME
    • President’s Perspective
  • Search

New Study Raises Cardiovascular Questions about Febuxostat for Gout

Lara C. Pullen, PhD  |  April 30, 2018

Updated May 2, 2018, to correct an error in how we presented the data from the study.

ad goes here:advert-1
ADVERTISEMENT
SCROLL TO CONTINUE

Gout brings with it significant comorbidities, which include cardiovascular disease. Although many patients respond well to the purine analogue, allopurinol, physicians also frequently prescribe xanthine oxidase inhibitors to help manage hyperuricemia. Unfortunately, the prescription of xanthine oxidase inhibitors, such as febuxostat, is done in the absence of large, randomized clinical trials examining the cardiovascular safety of this class of drugs.

Recently, William B. White, MD, professor of medicine at the University of Connecticut School of Medicine, and colleagues designed a noninferiority study to compare the cardiovascular safety of febuxostat and allopurinol. They found that, although febuxostat was noninferior to allopurinol with respect to rates of adverse cardiovascular events, all-cause mortality and cardiovascular mortality were higher in the patients treated with febuxostat compared with patients treated with allopurinol. The results of their Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARE) trial were published on March 12 in the New England Journal of Medicine.1

ad goes here:advert-2
ADVERTISEMENT
SCROLL TO CONTINUE

The researchers randomized a total of 6,190 patients in North America to receive either febuxostat or allopurinol. They followed the patients for a median of 32 months and a maximum of 85 months. The median duration of exposure to febuxostat was 728 days, and the median duration of exposure to allopurinol was 719 days. In the febuxostat group, 61% of patients received 40 mg febuxostat and 39% received 80 mg febuxostat daily as the final adjusted dose. In the allopurinol group, 21.8% of patients received 200 mg allopurinol, 44.6% received 300 mg allopurinol, 25.2% received 400 mg allopurinol, 4.3% received 500 mg allopurinol and 4.1% received 600 mg allopurinol. The proportion of patients with a serum urate level of less than 6.0 mg/dL was higher in the febuxostat group than in the allopurinol group at Week 2 and that difference persisted in later time points, although the finding was not significant.

The investigators note that many participants—approximately half from each study arm—discontinued their treatment and/or did not complete follow up. Specifically, 56.6% of patients discontinued the trial regimen and 45.0% discontinued follow up. The baseline characteristics of those patients who completed the trial visits and those who did not complete the trial visits were balanced.

The modified intention-to-treat analysis revealed that the primary endpoint (a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or unstable angina with urgent revascularization) occurred in 10.8% of febuxostat-treated patients and 10.4% of allopurinol-treated patients. These primary endpoint events occurred at a median period of 32 months. When the researchers performed a pre-specified analysis of events that occurred during receipt of the trial drug or within 30 days after discontinuation of treatment, they found that all-cause and cardiovascular mortality was higher in the febuxostat group than the allopurinol group, with a hazard ratio of 1.22 for cardiovascular death [95% confidence interval (CI), 1.01 to 1.47] and hazard ratio of 1.34 for cardiovascular death [95% CI, 1.03 to 1.73]. The results were similar when the investigators analyzed events that occurred while patients were being treated—as opposed to modified by the intention-to-treat analysis.

Page: 1 2 | Single Page
Share: 

Filed under:ConditionsGout and Crystalline Arthritis Tagged with:AllopurinolcardiovascularFebuxostathyperuricemiarisk

Related Articles

    Clinical Insights into Gout Management: Rheumatology Drugs at a Glance Pt. 4

    October 14, 2019

    Three clinical experts on gout offer their insights into common management errors, clinical pearls, new safety data from the FDA and the role of biologic therapies in the management of gout.

    Difficult Gout

    July 1, 2007

    “Grandpapa’s Torments” was the Rodnan Commemorative Gout Print featured at the 2005 ACR/ARHP Annual Scientific Meeting.

    FAST Results for Febuxostat Safety in Patients with Gout

    November 12, 2020

    ACR CONVERGENCE 2020—The results of a post-authorization study comparing the cardiovascular safety of febuxostat vs. allopurinol were presented in a late-breaking abstract session at the ACR’s fully virtual annual meeting on Monday, Nov. 9. Cardiologist Thomas MacDonald, MD, FRCP, MBChB, clinical professor (teaching and research) of molecular and clinical medicine, University of Dundee School of…

    Blacks, Asians at Higher Risk for Allopurinol-Related Skin Reactions

    September 8, 2016

    Be careful when prescribing allo­purinol to black and Asian gout patients, a study newly advises. Black and Asian patients who take this ubiquitous, more-than-40-year-old medication are at much higher risk of certain serious skin reactions than are Caucasians or Hispanics. Compared with Caucasians, blacks who take allopurinol to lower blood urate levels have an increased…

  • About Us
  • Meet the Editors
  • Issue Archives
  • Contribute
  • Advertise
  • Contact Us
  • Copyright © 2025 by John Wiley & Sons, Inc. All rights reserved, including rights for text and data mining and training of artificial technologies or similar technologies. ISSN 1931-3268 (print). ISSN 1931-3209 (online).
  • DEI Statement
  • Privacy Policy
  • Terms of Use
  • Cookie Preferences