The use of xanthine oxidoreductase inhibitors in slowing the progression of renal and cardiovascular disease. A summary of available clinical trials

Abstract

There is conflicting evidence whether elevated SUA is associated with or causes cardiovascular and renal disease. Identifying trials using xanthine oxidoreductase (XOR) inhibitors to reduce SUA might provide information on the epidemiological link between SUA and cardiovascular and renal disease.

The main objective is to provide a qualitative analysis of the available trials that studied the effect of XOR-inhibitors on cardiovascular and renal morbidity and mortality. EMBASE, MEDLINE and CENTRAL were systematically searched to identify relevant records.Articles in English published in peer reviewed journals reporting clinical trials using XOR-inhibitors on cardiovascular- and renal disease related end-points, including mortality. Studies on gout and surgical patients were excluded.

Titles and abstracts of the identified records were screened for eligibility. Relevant full-text articles were retrieved and main outcomes summarized in a modified PICO-table.

The thesis included 51 studies. Several studies reported reduced left ventricle mass(LVM) in the XOR-inhibitor group vs. placebo. In two studies on patients with congestive heart failure (CHF), assessing worsening of CHF, there was no effect of XOR inhibitors vs. placebo. Some studies reported slower progression of renal disease in the intervention arm. XOR-inhibitors reduced ambulatory blood pressure (BP) in pre-hypertensive and hypertensive adolescents in three small studies. There was a statistically significant effect of XOR-inhibitors on flow-mediated (endothelium dependent) vasodilatation in studies including participants with diabetes type 2, coronary artery disease and chronic kidney disease.

This thesis has identified a knowledge gap regarding the potential utility of SUA lowering drugs, XOR-inhibitors, to reduce the risk of cardiovascular and renal mortality and morbidity. Many small insufficiently powered studies have been conducted so far. There is possibly a potential for treating young subjects with newly developed hypertension with XOR-inhibitors. Well designed studies with clinically relevant end-points are highly called for.