Targeting inflammation in heart failure: evolving insights and future directions from randomized clinical trials

Heart failure (HF) is a leading cause of cardiovascular morbidity and mortality, with inflammation recognized as a key cause and byproduct. Despite observational studies linking elevated indices of inflammation with HF severity, as well as experimental models highlighting the centrality of inflammation to the pathogenesis of various types of HF, clinical trials of anti-inflammatory therapies in HF have produced inconsistent results. This variability may relate to the substrate included - differences in HF stage and/or clinical phenotype - as well as the mechanisms and target of therapeutics, whether aimed at preventing new-onset HF or treating established disease. This review evaluates clinical trials directly targeting inflammation in HF, with a focus on disease stage and symptomatology. Ultimately, by highlighting the importance of HF staging and the timing of therapeutics in prior inflammation-targeted interventions, we aim to inform more precise targets from a disease substrate perspective when designing trials of inflammation-modulating therapies in HF.