CARES
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
75.0% male
N = 6190
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%
10.4%
10.8 %
8.1 %
5.4 %
2.7 %
0.0 %
Febuxostat
Allopurinol
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority 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 CV 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 CV 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.
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