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Rischio cardiovascolare associato all’utilizzo di febuxostat o allopurinolo in pazienti con la gotta

Soggetti con la gotta hanno un rischio di evento cardiovascolare aumentato. In questo studio, pazienti con gotta e patologia cardiovascolare sono stati trattati con due inibitori della xantina ossidasi: febuxostat (inibitore non purinico) oppure con allopurinolo (inibitore a base purinica). In termini di eventi cardiovascolari avversi, Il trattamento con febuxostat o allopurinolo sono risultati paragonabili ma il tasso di mortalità per diverse cause o per eventi cardiovascolari è più alto in soggetti trattati con febuxostat rispetto a quelli con allopurinolo.

Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout

White WB, Saag KG, Becker MA, Borer JS, Gorelick PB, Whelton A, Hunt B, Castillo M, Gunawardhana L, CARES Investigators

N Engl J Med. 2018;378:1200-1210

BACKGROUND: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.

N Engl J Med. 2018;378:1200-1210