ORLANDO, Fla. — Febuxostat was noninferior to allopurinol in terms of adverse CV event rates in patients with gout and major CV coexisting conditions, according to the results of the CARES study presented at the American College of Cardiology Scientific Session.
However, those assigned febuxostat (Uloric, Takeda) had higher rates of CV death and all-cause death than those assigned allopurinol.
"Gout affects approximately 8.3 million people in the United States and is predominantly a disease in men ... and a very high proportion of those with gout also have comorbid illnesses of cardiovascular nature," William B. White, MD, from the University of Connecticut School of Medicine, Farmington, said at a press conference. "The study that we conducted over the last several years was to evaluate the safety of these two most commonly used preventive therapies, that is xanthine oxidase inhibitors febuxostat and allopurinol."
White and colleagues conducted a multicenter, double-blind, noninferiority trial comprised of patients with gout and CVD.
A total of 6,190 patients were randomly assigned to receive febuxostat or allopurinol and were stratified according to kidney function.
There was a prespecified noninferiority margin of 1.3 for the HR for the primary endpoint, which was a composite of CVD, nonfatal MI, nonfatal stroke or unstable angina with urgent revascularization.
Patients were followed for a median of 32 months after randomization.
Over half of the patients in the trial had their regimen discontinued and 45% of patients discontinued follow-up, White said.
The researchers conducted a modified intention-to-treat analysis which showed a primary endpoint event occurred in 10.8% of the febuxostat group and in 10.4% of the allopurinol group (HR = 1.03; upper limit of the one-sided 98.5% CI, 1.23; P = .002 for noninferiority).
All-cause and CV mortality were higher among those in the febuxostat cohort compared with the allopurinol group (HR for all-cause death = 1.22; 95% CI, 1.01-1.47; HR for CV death = 1.34; 95% CI, 1.03-1.73).
"Further analyses from the trial are ongoing to evaluate the unexpected mortality findings in CARES,” White said.
In a press conference, Cardiology Today Editorial Board Member Karol E. Watson, MD, PhD, professor of medicine/cardiology at the David Geffen School of Medicine at the University of California, Los Angeles, and director of the UCLA Women’s Cardiovascular Health Center, said the study “did drive home what we now know: you have to evaluate the cardiovascular safety of a lot of these non-cardiac drugs. ... I very much appreciate this well-conducted study and what we can learn from it.” – by Dave Quaile
White, WB, et al. ACC/NEJM Late-Breaking Clinical Trials. Presented at: American College of Cardiology Scientific Session; March 10-12, 2018; Orlando, Fla.
White, WB, et al. NEJM. 2018;doi:10. 1056/NEJMoa1710895.
Disclosure: The study was funded by Takeda Development Center Americas. White reports receiving personal fees from AstraZeneca Abbvie, GSK, Novartis, Pfizer and Takeda USA.