Topiroxostat versus allopurinol in patients with chronic heart failure complicated by hyperuricemia: A prospective, randomized, open-label, blinded-end-point clinical trial

Abstract

Background The benefits of xanthine oxidase inhibitors to chronic heart failure (CHF) patients is controversial. We investigated the beneficial effects of a novel xanthine oxidoreductase inhibitor, topiroxostat, in patients with CHF and hyperuricemia (HU), in comparison to allopurinol. Methods and results The prospective, randomized open-label, blinded-end-point study was performed in 141 patients with CHF and HU at 4 centers. Patients were randomly assigned to either topiroxostat or allopurinol group to achieve target uric acid level ≤6.0 mg/dL. According to the protocol, 140 patients were followed up for 24 weeks. Percent change in ln (N-terminal-proB-type natriuretic peptide) at week 24 (primary endpoint) was comparable between topiroxostat and allopurinol groups (1.6±8.2 versus -0.4±8.0%; P = 0.17). In the limited number of patients with heart failure with reduced ejection fraction (HFrEF) (left ventricle ejection fraction <45%), ratio of peak early diastolic flow velocity at mitral valve leaflet to early diastolic mitral annular motion velocity (E/e’) decreased in topiroxostat group, but not in allopurinol group. Urinary 8-hydroxy-2’-deoxyguanosine and L-type fatty acid-binding protein levels increased and osmolality decreased significantly in allopurinol group, while these changes were less or absent in topiroxostat group. In allopurinol group HFrEF patients, additional to the increases in these urinary marker levels, urinary creatinine levels decreased, with no change in clearance, but not in topiroxostat group. Conclusions Compared with allopurinol, topiroxostat did not show great benefits in patients with CHF and HU. However, topiroxostat might have potential advantages of reducing left ventricular end-diastolic pressure, not worsening oxidative stress in proximal renal tubule, and renoprotection over allopurinol in HFrEF patients.

Evaluation of the therapeutic role of allopurinol on bisphenol S gastric and renal toxicity in adult male albino rats: An in vivo study

“…Allopurinol significantly normalised and reversed changes in the serum levels of antioxidants and the lipid peroxidation marker in hyperuricemic mice through downregulation of XO, a major source of free radicals, indicating its antioxidant role, 31,38 and it also significantly reduced urinary 8-OHdG levels. 39,40 These findings align with our own. This is the first study to demonstrate the harmful effects of low and high doses of BPS on the stomach and kidneys of rats.…”

Food-derived bio-functional peptides for the management of hyperuricemia and associated mechanism

“…headache and renal, hepatic and gastrointestinal abnormalities [1] . Besides, topiroxostat, known as a novel XOD inhibitor, was under preclinical study [14] . In addition, purine nucleoside phosphorylase (PNP) was a new clinical target for uric acid management, and its inhibitor BCX4208 is in early clinical investigation in gout treatment [15] (Table 1).…”

Role of hyperuricemia in cardiovascular disease and its treatment options: A review article

“…Interestingly, topiroxostat did not exhibit significant advantages over allopurinol in patients with CHF and HU. However, topiroxostat may be preferable to allopurinol in HF with reduced ejection fraction (HFrEF) patients due to its possible benefits in lowering left ventricular end-diastolic pressure, preventing aggravation of oxidative stress in the proximal renal tubule, and renoprotection (24).…”