Febuxostat increases the risk of heart-related and all- cause death compared with allopurinol in patients with gout, according to a large safety trial. Healthcare professionals are advised by the US Food and Drug Administration (FDA) to:
Prescribe febuxostat only for patients who have failed treatment with or can not tolerate allopurinol
Counsel patients regarding the cardiovascular risk with febuxostat and advise them to seek medical attention immediately if they experience chest pain, shortness of breath, rapid or irregular heartbeat, numbness or weakness on one side of their body, dizziness, trouble speaking, or sudden severe headache.
In 2009, febuxostat was approved by the FDA to treat gout, but with a warning and precaution regarding possible cardiovascular events. The manufacturer was required to conduct a large postmarketinging safety clinical trial.
The double-blind study (CARES) compared cardiovascular outcomes in patients with gout and major cardiovascular disease (n = 6198) who were randomized to febuxostat or to allopurinol. Treatment groups did not differ with respect to a primary composite outcome of cardiovascular events. However, cardiovascular death and all-cause mortality were significantly more common among patients taking febuxostat than allopurinol (4.3% vs. 3.2%, HR 1.34 [95% CI 1.03 to 1.73]; 7.8% vs. 6.4%, HR 1.22 [95% CI 1.01 to 1.47], respectively).See Management: approach See Management: treatment algorithm
Acute onset of severe joint pain.
Swelling, effusion, warmth, erythema and/or tenderness of the involved joint(s).
Arthrocentesis with synovial fluid analysis shows strongly negative birefringent needle-shaped crystals under polarized light.
Nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, or corticosteroids are used to treat acute disease.
Allopurinol, febuxostat, probenecid, or lesinurad may be used as uric acid-lowering drugs when long-term prevention of crystal deposition is indicated.
Complications include joint destruction, kidney disease, and urolithiasis.
Gout is a syndrome characterized by: hyperuricemia and deposition of urate crystals causing attacks of acute inflammatory arthritis; tophi around the joints and possible joint destruction; renal glomerular, tubular, and interstitial disease; and uric acid urolithiasis. The disease most commonly affects the first toe (podagra), foot, ankle, knee, fingers, wrist, and elbow; however, it can affect any joint.
Harvard Medical School
Director of the Musculoskeletal Medicine Unit
Department of Orthopedics & Division of Rheumatology
Beth Israel Deaconess Medical Center
FB declares that he has no competing interests.
Professor of Medicine
VA Medical Center
HRS has been a consultant for a number of pharmaceutical companies that produce drugs that can be used for the treatment of gout. Some companies have supplied HRS with funding. HRS is an author of a number of references cited in this monograph.
Associate Director of Teaching and Honorary Senior Lecturer in Rheumatology
Academic Rheumatology Group
Faculty of Medicine
University of Sheffield
AA declares that he has no competing interests.
Professor of Primary Care Research
Warwick Medical School
MU declares that he has no competing interests.
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