Does antagonizing inflammatory mediators improve outcomes in patients with heart failure?
Despite experimental evidence linking inflammation to ventricular remodeling, phase III trials of anti-inflammatory therapies in heart failure have been negative, necessitating a deeper understanding of innate immunity.
Elevated levels of inflammatory mediators have been identified in patients with heart failure, including heart failure with reduced and preserved ejection fraction, as well as acute decompensated heart failure. Moreover, experimental studies have shown repeatedly that activation of inflammation in the heart provokes left ventricular remodeling and left ventricular dysfunction. Nonetheless, phase III clinical trials that have attempted to antagonize inflammatory mediators have been negative with respect to the primary end points of the trials, and in some patients, resulted in worsening heart failure or death. The following review will discuss how recent developments in the field of innate immunity have advanced our understanding of the role of inflammation in the pathogenesis of heart failure and will discuss the negative outcomes of the existing clinical trials in light of this new information.
Douglas L. Mann (Fri,) studied this question.