The Potential Role of Anti-Inflammatory Therapy in Heart Failure Treatment

Heart failure (HF) remains a prevalent global health challenge and burden, prompting researchers to seek further therapies that provide morbidity and mortality benefits in this patient population. In recent years, the development of proven pharmacotherapeutics has stalled partly due to the continued poor understanding of the various underlying mechanisms of HF. However, a potential therapeutic target has emerged after recent evidence identified the role of inflammation in the pathogenesis of HF. Systemic and myocardial inflammation caused by activation of specific inflammasomes and the subsequent production of downstream cytokines, including interleukins and tumor necrosis factor, contribute to cardiomyocyte dysfunction, fibroblast activation, and extracellular matrix deposition and fibrosis. A key driver, the inflammasome is activated in cases of myocardial infarction, pressure overload, and sympathetic overactivation, subsequently leading to cardiac hypertrophy, fibrosis, and pyroptosis. Additionally, chronic inflammation driven by factors such as oxidative stress, metabolic disturbances, and neurohormonal activation leads to adverse cardiac remodeling and impaired myocardial function, with the inflammatory processes likely representing a common final pathway in the pathophysiology of HF. To target these pathways, numerous anti-inflammatory therapies, originally approved for other conditions, have been investigated for a potential benefit in HF. While previous small studies of these anti-inflammatory therapies in HF showed limited potential benefit, many of these trials were ultimately inconclusive. Therefore, multiple larger trials have subsequently investigated these anti-inflammatory therapies, including a novel agent targeting a critical inflammasome, to better elucidate the role, if any, of these medications in the treatment of HF.