Myeloperoxidase inhibition in the landscape of anti-inflammatory therapies for heart failure with preserved ejection fraction: the ENDEAVOR trial.

Abstract

Systemic inflammation is considered one of the key physiological drivers in heart failure with preserved ejection fraction (HFpEF) and is associated with worse outcomes. While inflammation has been investigated as a potential therapeutic target in HFpEF, previous trials evaluating treatments targeting various inflammatory pathways such as interleukin-1 (IL-1) inhibitors or colchicine have largely yielded neutral effects on clinical outcomes. Myeloperoxidase (MPO), found primarily in neutrophils, contributes to inflammation by generating reactive oxygen species (ROS), leading to adverse cardiac remodeling and endothelial dysfunction. This review summarizes the findings of the ENDEAVOR trial evaluating the efficacy and safety of mitiperstat, a selective MPO inhibitor, in patients with symptomatic HF with ejection fraction > 40%. We will discuss these results within the context of previous anti-inflammatory trials in HF and explore the challenges in developing effective anti-inflammatory therapies for this complex condition.