Myeloperoxidase inhibition with mitiperstat in heart failure with preserved or mildly reduced ejection fraction: a randomized phase 2b trial.

Mitiperstat, an MPO inhibitor, did not improve symptoms or exercise capacity in 711 patients with heart failure and preserved or mildly reduced ejection fraction over 48 weeks.

• Why it matters: Heart failure with preserved or mildly reduced ejection fraction involves mechanisms like microvascular dysfunction and fibrosis, driven by MPO-derived oxidants, which are potential therapeutic targets. Addressing this gap could lead to better treatments for this common and challenging condition.
• What they did: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial tested 711 patients assigned to mitiperstat (2.5 mg or 5 mg) or placebo, measuring symptom scores, exercise capacity, biomarkers, and echocardiographic parameters over 48 weeks.
• The result: Mitiperstat was safe and well tolerated but showed no significant benefit in improving symptoms, exercise function, or secondary markers, suggesting MPO inhibition alone may not be effective for this patient population.