Analysis: No Cardiovascular Benefits for Xanthine Oxidase Inhibitors

SAN FRANCISCO, CA—Xanthine oxidase inhibitors (XOIs) do not improve uric acid-associated risks for cardiovascular events or deaths among adults, according to a meta-analysis of data pooled from 61 randomized controlled clinical studies, which was reported at the 2015 ACR/ARHP Annual Meeting.

"A meta-analysis of randomized controlled trials performed in different clinical contexts failed to demonstrate a protective effect of XOIs on the incidence of major cardiovascular events, death, or any adverse cardiovascular event," reported lead study author Markus Bredemeier, MD, of the Rheumatology Division, Hospital Nossa Senhora da Conceição - Grupo Hospital Conceição, in Porto Alegre, Brazil. “A small but statistically significant increase in the risk of skin rash was observed in the XOI group.” 

Earlier observational studies had suggested that XOIs might reduce major adverse cardiovascular events (MACE) risks, the coauthors noted. They conducted the meta-analysis in order to confirm those findings, because observational study findings are often confounded by selection bias and other problems.

Dr. Bredemeier and his coauthors searched numerous research literature databases for randomized controlled trials that compared XOIs with placebo or no treatment, for 4 weeks or longer. Studies that included patients younger than age 18 years were excluded from the analysis.

A total of 61 randomized controlled trials were included in the meta-analysis, representing approximately 5,500 patients, Dr. Bredemeier reported.

Outcomes analyzed were “the incidence of MACE (cardiovascular death, non-fatal myocardial infarction, unstable angina requiring urgent revascularization, or non-fatal stroke) and mortality; total cardiovascular events (TCE), serious adverse events (SAE), and skin rash served as secondary outcomes.” Odds ratios (ORs) were calculated and a subgroup analysis was performed “including only studies in which subjects were at high-risk for cardiovascular events.”  

“The use of XOI was not significantly associated with the risk of MACE (OR 1.24; 95%CI: 0.54–2.85, P=0.61), death (OR 0.93; 0.49–1.75; P=0.82), total cardiovascular events (OR 0.83; 0.59–1.18; P=0.31), and SAE (OR 0.99; 0.74–1.33; P=0.95),” they researchers reported. 

“The risk of skin rash was higher in the XOI group (OR 2.18; 1.26–3.77; P=0.005),” Dr. Bredemeier reported. "In a subgroup analysis of studies including mainly individuals with high cardiovascular risk profiles, there were no significant differences in the risk of MACE (OR 1.05; 0.44–2.50; P=0.92), TCE (OR 0.79; 0.57–1.11; P=0.18), or death (OR 0.88; 0.46–1.67; P=0.70).”

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