6/28/23, 12:03 AM CARES Pathway Feedback Search Clinical Topics Home Studies CARES CARES Disease Gout Trial question Is febuxostat noninferior to allopurinol in patients with gout and major cardiovascular coexisting conditions? Study design Multi-center Double blinded RCT Population Characteristics of study participants 25.0% female N = 6190 75.0% male 6190 patients (1534 female, 4656 male) Inclusion criteria: patients with gout and major cardiovascular coexisting conditions Key exclusion criteria: secondary hyperuricemia due to myeloproliferative disorder, xanthinuria, active peptic ulcer disease, history of cancer, receiving urate-lowering therapy Interventions N=3098 febuxostat (adjusted according to serum urate) N=3092 allopurinol (adjusted according to kidney function) Primary outcome CV death, nonfatal MI, nonfatal CVA, or UA requiring urgent revascularization 10.8 % 10.8 10.4 8.1 % https://web.pathway.md/studies/recC9STYXflKFyvqG 1/2 6/28/23, 12:03 AM CARES Pathway 5.4 % Difference not exceeding nonferiority margin 2.7 % 0.0 % Febuxostat Allopurinol Difference not exceeding nonferiority margin in CV death, nonfatal MI, nonfatal CVA, or UA requiring urgent revascularization (10.8% vs. 10.4%; HR 1.03, 95% CI 0.38 to 1.68) Secondary outcomes Significant increase in death from any cause (7.8% vs. 6.4%; HR 1.22, 95% CI 1.01 to 1.47) Significant increase in cardiovascular death (4.3% vs. 3.2%; HR 1.34, 95% CI 1.03 to 1.73) Safety outcomes No significant difference in overall rates of adverse major cardiovascular events. Conclusion In patients with gout and major cardiovascular coexisting conditions, febuxostat was noninferior to allopurinol with respect to CV death, nonfatal MI, nonfatal CVA, or UA requiring urgent revascularization. All-cause mortality and cardiovascular mortality were higher with febuxostat than with allopurinol. Reference White WB, Saag KG, Becker MA et al. Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. N Engl J Med. 2018 Mar 29;378(13):1200-1210. Open reference URL https://web.pathway.md/studies/recC9STYXflKFyvqG 2/2