Effects of topiroxostat administration on brain natriuretic peptide levels in heart failure patients with a preserved ejection fraction: A pilot study.

BACKGROUND Various optimal medical therapies have been established for the treatment of heart failure (HF) with a reduced ejection fraction (HFrEF). Like HFrEF, HF with a preserved ejection fraction (HFpEF) too is related to poor prognoses. We aimed to investigate the effect of topiroxostat, an oral xanthine oxidoreductase inhibitor, in HFpEF patients with hyperuricemia or gout. METHODS In this non-randomized, 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 the rate of change in the log-transformed brain natriuretic peptide (BNP) levels from the baseline to 24 weeks after topiroxostat treatment. The secondary outcomes included the amount of change in the BNP levels, 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 The log-transformed BNP levels decreased by -3.4 ± 8.9 % (p = 0.043) after 24 weeks of topiroxostat treatment. The rate of change in the BNP level decreased (-18.0 [-57.7, 4.0] pg/ml, p = 0.041). The 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, -2.3 ± 3.7 ng/mgCr, p = 0.009, respectively). CONCLUSIONS The BNP levels were significantly lowered 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.