The failure of immunomodulation therapy in heart failure: does the statins "paradigm" prove the rule?

Inflammation is an important process and an underlying mechanism involved in atherogenesis as well as the clinical manifestations following coronary artery disease (CAD). Evidence suggests that chronic heart failure (CHF) is associated with an increased inflammatory process. Pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-a), interleukin-6 (IL-6), interleukin-1 (IL-1) and adhesion molecules are elevated in states of CHF and are related to long term prognosis. Statins are among the most effective compounds reducing morbidity and mortality in patients with, or at increased risk of, CAD. Efficacy and safety of statin treatment has not been validated in patients with CHF. Several studies have reported that statins could be beneficial in patients with CHF. In addition, the beneficial effects of statins have been largely attributed to their anti-inflammatory properties. However, recent randomized, double-blind, placebo-controlled trials reported that statins did not affect clinical outcomes in patients with CHF of any cause. These data support the notion that current immunomodulation approaches in heart failure are not successful. Thus, more large scale clinical trials are required to evaluate the impact of statins on immune imbalance and its restoration in patients with CHF.