Cardiovascular safety associated with febuxostat versus allopurinol among patients with gout: Update with accumulated use of febuxostat. 2022

Anna Shin, and Se Rim Choi, and Minji Han, and You-Jung Ha, and Yun Jong Lee, and Eun Bong Lee, and Eun Ha Kang
Division of Rheumatology Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

To re-evaluate comparative cardiovascular (CV) safety of febuxostat versus allopurinol among patients with gout following recent accumulated use of febuxostat. Using 2011-2019 Korea National Health Insurance database, we conducted a cohort study comparing gout patients initiating febuxostat versus allopurinol, 1:1 matched on a propensity-score (PS) for >60 covariates. The primary outcome was a composite endpoint of myocardial infarction, coronary revascularization, and stroke. Secondary outcomes were individual components of the primary outcome, hospitalized heart failure, and all-cause mortality. Subgroup analyses were done for those at high CV risk, long-term users (follow-up >3 years), and those without chronic kidney disease. We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We included 160,930 PS-matched pairs of febuxostat and allopurinol users (mean age 59.3 years, 79.6% male). Incidence rates of the primary outcome were 2.06 and 2.27 per 100 person-years for febuxostat and allopurinol users, respectively, with a HR [95% CI] of 1.03 [0.95-1.12] comparing febuxostat versus allopurinol initiators. We also observed similar risks for secondary outcomes, except for reduced all-cause mortality among febuxostat users (HR [95% CI] of 0.84 [0.78-0.91]). Subgroup analyses also showed non-inferior CV safety of febuxostat. In this population-based cohort study including the largest number of febuxostat users to date, we found non-inferior CV safety of febuxostat versus allopurinol. There was a 16% reduction in all-cause mortality among febuxostat users.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009203 Myocardial Infarction NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION). Cardiovascular Stroke,Heart Attack,Myocardial Infarct,Cardiovascular Strokes,Heart Attacks,Infarct, Myocardial,Infarction, Myocardial,Infarctions, Myocardial,Infarcts, Myocardial,Myocardial Infarctions,Myocardial Infarcts,Stroke, Cardiovascular,Strokes, Cardiovascular
D005260 Female Females
D006073 Gout Metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of URIC ACID calculi. Gouts
D006074 Gout Suppressants Agents that increase uric acid excretion by the kidney (URICOSURIC AGENTS), decrease uric acid production (antihyperuricemics), or alleviate the pain and inflammation of acute attacks of gout. Antigout Agents,Antihyperuricemic,Antihyperuricemics,Agents, Antigout,Suppressants, Gout
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000069465 Febuxostat A thiazole derivative and inhibitor of XANTHINE OXIDASE that is used for the treatment of HYPERURICEMIA in patients with chronic GOUT. 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid,TEI 6720,TEI-6720,Uloric,6720, TEI,TEI6720
D000493 Allopurinol A XANTHINE OXIDASE inhibitor that decreases URIC ACID production. It also acts as an antimetabolite on some simpler organisms. Allohexal,Allohexan,Alloprin,Allopurin,Allorin,Allpargin,Allural,Apulonga,Apurin,Atisuril,Bleminol,Caplenal,Capurate,Cellidrin,Embarin,Foligan,Hamarin,Jenapurinol,Lopurin,Lysuron,Milurit,Milurite,Novopurol,Pan Quimica,Progout,Pureduct,Purinol,Remid,Rimapurinol,Roucol,Suspendol,Tipuric,Uribenz,Uridocid,Uripurinol,Urosin,Urtias,Xanthomax,Xanturic,Zygout,Zyloprim,Zyloric
D015331 Cohort Studies Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. Birth Cohort Studies,Birth Cohort Study,Closed Cohort Studies,Cohort Analysis,Concurrent Studies,Historical Cohort Studies,Incidence Studies,Analysis, Cohort,Cohort Studies, Closed,Cohort Studies, Historical,Studies, Closed Cohort,Studies, Concurrent,Studies, Historical Cohort,Analyses, Cohort,Closed Cohort Study,Cohort Analyses,Cohort Studies, Birth,Cohort Study,Cohort Study, Birth,Cohort Study, Closed,Cohort Study, Historical,Concurrent Study,Historical Cohort Study,Incidence Study,Studies, Birth Cohort,Studies, Cohort,Studies, Incidence,Study, Birth Cohort,Study, Closed Cohort,Study, Cohort,Study, Concurrent,Study, Historical Cohort,Study, Incidence

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