Key result
Topiroxostat administration for 24 weeks significantly reduced log-transformed brain natriuretic peptide levels by 3.4% from baseline in patients with heart failure with preserved ejection fraction and hyperuricemia or gout.
Why the study?
While optimal medical therapies are established for HFrEF, both HFrEF and HFpEF carry poor outcomes, motivating investigation into the effect of topiroxostat in HFpEF patients with hyperuricemia or gout.
Does topiroxostat reduce BNP levels in patients with HFpEF and hyperuricemia or gout?
Does topiroxostat reduce BNP levels in patients with HFpEF and hyperuricemia or gout?
Topiroxostat administration significantly lowered BNP and uric acid levels in HFpEF patients with hyperuricemia or gout, though the absolute reduction in BNP was small.
Topiroxostat was associated with modest BNP reduction in HFpEF; hypothesis-generating and requires RCTs before practice change.
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.
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A 2021 study studied Heart failure with preserved ejection fraction (HFpEF) with hyperuricemia or gout (n=33). Topiroxostat vs. Baseline was evaluated on Rate of change in log-transformed brain natriuretic peptide (BNP) level from baseline to 24 weeks (-3.4%, p=0.043). Topiroxostat administration for 24 weeks significantly reduced log-transformed brain natriuretic peptide levels by 3.4% from baseline in patients with heart failure with preserved ejection fraction and hyperuricemia or gout.
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