Journal of Rheumatic Diseases

Table. 2.

Representative studies for CV related mortality risk between febuxostat and allopurinol or placebo

Design Population Exposure comparator End points CV outcome (febuxostat compared to allopurinol)
RCT/White et al. [45] Gout with CVD Febuxostat (n=3,098) Allopurinol (n=3,092) CV death, nonfatal MI, stroke, revascularization CV mortality (HR 1.34, 95% CI 1.03∼1.73)
All-cause mortality (HR 1.22, 95% CI 1.01∼1.47)
Cohort/Su et al. [51] Gout Febuxostat (n=44,111) Allopurinol (n=44,111) MACEs, VTE, HF/AF, CV death, all-cause mortality CV mortality (HR 1.19, 95% CI 1.03∼1.36)
HF (HR 1.22, 95% CI 1.13∼1.33)
SR & Meta-analysis/Cuenca et al. [52] 25 RCT and 10 meta-analysis Febuxostat (n=8,602) Allopurinol (n=5,118) MACE & CV mortality CV death (RR 1.29, 95% CI 1.01∼1.66), (if, excluded CARES [RR 0.73, 95% CI 0.24∼2.25])
Cohort/Zhang et al. [53] Gout(Medicare data) Febuxostat (n=24,936) Allopurinol (n=74,808) MI or stroke, HF, all-cause mortality All-cause mortality (HR 0.95, 95% CI 0.89∼1.02)
HF exacerbation (HR 0.93)
Cohort/Ju et al. [54] Gout (Hong Kong) Febuxostat (n=276) Allupurinol (n=828) MACE all-cause mortality All-cause mortality (HR 0.99, 95% CI 0.73∼1.33)
Cohort/Kang et al. [55] Gout (KNHIS) Febuxostat (n=9,910) Allopurinol (n=39,640) MI/Stroke/TIA attack or revascularization, mortality All-cause mortality (HR 0.96, 95% CI 0.79∼1.16)
RCT/Kimura et al. [56] Hyperuricemia with CKD 3 Febuxostat (n=219) Placebo (n=222) Renal function and CV event No difference for death
Cohort/Chen et al. [57] Gout Febuxostat (n=5,278) Allopurinol (n=5,278) Hypersensitivity, CVD CVD risk (HR 1.16, 95% CI 0.95∼1.41)
Cohort/Foody et al. [58] Gout with CKD 3 or 4 and CVD Febuxostat (n=370) Allopurinol (n=2,056) Major CV event Major CV event (HR 0.52, 95% CI 0.30∼0.91)
RCT/Kojima et al. [59] Hyperuricemia with CV or renal disease Febuxostat (n=537) Others (n=537) Fatal and non-fatal CV, renal event and death All-cause mortality (HR 0.75, 95% CI 0.59∼0.95)

CV: cardiovascular, RCT: randomized controlled trial, SR: systematic review, CVD: cardiovascular disease, KNHIS: Korean National Health Insurance Service, CKD: chronic kidney disease, MI: myocardial infarction, MACE: major adverse cardiac event, VTE: venous thromboembolism, HF: heart failure, AF: atrial fibrillation, TIA: transient ischemic attack, HR: hazard ratio, CI: confidence interval, RR, relative risk, CARES: the Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout.

J Rheum Dis 2020;27:78~87
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