Effect of topiroxostat on brain natriuretic peptide level in patients with heart failure with preserved ejection fraction: A pilot study

Abstract

Background: Various optimal medical therapies have been established to treat heart failure (HF) with reduced ejection fraction (HFrEF). Both HFrEF and HF with preserved ejection fraction (HFpEF) are associated with poor outcomes. We investigated the effect of topiroxostat, an oral xanthine oxidoreductase inhibitor, for HFpEF patients with hyperuricemia or gout. Methods: In this nonrandomized, open-label, single-arm trial, we administered topiroxostat 40-160 mg/ day to HFpEF patients with hyperuricemia or gout to achieve a target uric acid level of 6.0 mg/dL. The primary outcome was rate of change in log-transformed brain natriuretic peptide (BNP) level from baseline to 24 weeks after topiroxostat treatment. The secondary outcomes included amount of change in BNP level, uric acid evaluation values, and oxidative stress marker levels after 24 weeks of topiroxostat treatment. Thirty-six patients were enrolled; three were excluded before study initiation. Results: Change in log-transformed BNP level was －3.4 ± 8.9% (p = 0.043) after 24 weeks of topiroxostat treatment. The rate of change for the decrease in BNP level was －18.0 (－57.7, 4.0 pg/mL; p = 0.041). Levels of uric acid and 8-hydroxy-2’-deoxyguanosine/creatinine, an oxidative stress marker, also significantly decreased (－2.8 ± 1.6 mg/dL, p < 0.001, and －2.3 ± 3.7 ng/mgCr, p = 0.009, respectively). Conclusions: BNP level was significantly lower in HFpEF patients with hyperuricemia or gout after topiroxostat administration; however, the rate of decrease was low. Further trials are needed to confirm our findings. (J Nippon Med Sch 2021; 88: 423―431).