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Effects of xanthine oxidase inhibitors on cardiovascular disease in patients with gout: a cohort study.

ABSTRACT: Hyperuricemia and gout are associated with an increased risk of cardiovascular disease (CVD). It is unknown whether treating hyperuricemia with xanthine oxidase inhibitors (XOIs), including allopurinol and febuxostat, modifies cardiovascular risks.We used US insurance claims data to conduct a cohort study among gout patients, comparing XOI initiators with non-users with hyperuricemia defined as serum uric acid level ?6.8 mg/dL. We calculated incidence rates of a composite nonfatal cardiovascular outcome that included myocardial infarction, coronary revascularization, stroke, and heart failure. Propensity score (PS)-matched Cox proportional hazards regression compared the risk of composite cardiovascular endpoint in XOI initiators vs those with untreated hyperuricemia, controlling for baseline confounders. In a subgroup of patients with uric acid levels available, PS-matched Cox regression further adjusted for baseline uric acid levels.There were 24,108 PS-matched pairs with a mean age of 51 years and 88% male. The incidence rate per 1000 person-years for composite CVD was 24.1 (95% confidence interval [CI] 22.6-26.0) in XOI initiators and 21.4 (95% CI, 19.8-23.2) in the untreated hyperuricemia group. The PS-matched hazard ratio for composite CVD was 1.16 (95% CI, 0.99-1.34) in XOI initiators vs those with untreated hyperuricemia. In subgroup analyses, the PS-matched hazard ratio for composite CVD adjusted for serum uric acid levels was 1.10 (95% CI, 0.74-1.64) among XOI initiators.Among patients with gout, initiation of XOI was not associated with an increased or decreased cardiovascular risk compared with those with untreated hyperuricemia. Subgroup analyses adjusting for baseline uric acid levels also showed no association between XOI and cardiovascular risk.

SUBMITTER: Kim SC

PROVIDER: S-EPMC4442710 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Effects of xanthine oxidase inhibitors on cardiovascular disease in patients with gout: a cohort study.

Kim Seoyoung C SC Schneeweiss Sebastian S Choudhry Niteesh N Liu Jun J Glynn Robert J RJ Solomon Daniel H DH

The American journal of medicine 20150203 6

<h4>Background</h4>Hyperuricemia and gout are associated with an increased risk of cardiovascular disease (CVD). It is unknown whether treating hyperuricemia with xanthine oxidase inhibitors (XOIs), including allopurinol and febuxostat, modifies cardiovascular risks.<h4>Methods</h4>We used US insurance claims data to conduct a cohort study among gout patients, comparing XOI initiators with non-users with hyperuricemia defined as serum uric acid level ≥6.8 mg/dL. We calculated incidence rates of ...[more]

PMID: 25660249

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Project description:Xanthine oxidase inhibitors (XOI), classified as purine-like (allopurinol and oxypurinol) and non-purine (febuxostat and topiroxostat) XOI, present antioxidant properties by reducing the production of reactive oxygen species derived from purine metabolism. Oxidative stress is an important factor related to endothelial dysfunction and ischemia-reperfusion injury, and may be implicated in the pathogenesis of heart failure, hypertension, and ischemic heart disease. However, there is contradictory evidence regarding the possible cardiovascular (CV) protective effect exerted by XOI. Our objective is to compare the incidence of major adverse cardiovascular events (MACE), mortality, total (TCE) and specific CV events in randomized controlled trials (RCTs) testing XOI against placebo or no treatment.PubMed, EMBASE, Web of Science, Cochrane Central, Lilacs databases were searched from inception to Dec 30 2016, along with hand searching. RCTs including exclusively adult individuals, lasting ??4 weeks, with no language restriction, were eligible. Independent paired researchers selected studies and extracted data. Considering the expected rarity of events, Peto and DerSimonian/Laird odds ratios (OR), the latter in case of heterogeneity, were used for analysis. Random-effects meta-regression was used to explore heterogeneity.The analysis of MACE included 81 articles (10,684 patients, 6434 patient-years). XOI did not significantly reduce risk of MACE (ORP =?0.71, 95% CI 0.46-1.09) and death (0.89, 0.59-1.33), but reduced risk of TCE (0.60, 0.44-0.82; serious TCE: 0.64, 0.46 to 0.89), and hypertension (0.54, 0.37 to 0.80). There was protection for MACE in patients with previous ischemic events (0.42, 0.23-0.76). Allopurinol protected for myocardial infarction (0.38, 0.17-0.83), hypertension (0.32, 0.18-0.58), TCE (0.48, 0.31 to 0.75, I2 =?55%) and serious TCE (0.56, 0.36 to 0.86, I2 =?44%). Meta-regression associated increasing dose of allopurinol with higher risk of TCE and serious TCE (P?<?0.05). Accordingly, lower doses (??300 mg/day) of allopurinol reduced the risk of TCE, unlike higher doses. Non-purine-like XOI did not significantly reduce or increase the risk of adverse CV events, but confidence intervals were wide. Quality of evidence was generally low to moderate.Purine-like XOI may reduce the incidence of adverse CV outcomes. However, higher doses of allopurinol (>?300 mg/day) may be associated with loss of CV protection.

Dataset Information

Effects of xanthine oxidase inhibitors on cardiovascular disease in patients with gout: a cohort study.

Publications

Effects of xanthine oxidase inhibitors on cardiovascular disease in patients with gout: a cohort study.

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