Endothelin antagonists for chronic heart failure: do they have a role?

The development of novel and more effective therapeutic strategies for chronic heart failure is an important priority in cardiovascular medicine. Although much has still to be learned about the role of ET-1 in human physiology, current evidence suggests an important role for the peptide in the pathophysiology of chronic heart failure. It may not be the vasodilatory effect of these agents which provides long-term benefit in chronic heart failure, but the ability of these agents to alter neuro-hormonal activation, or to delay or regress the adverse left ventricular remodelling and vascular changes that are characteristic of chronic heart failure. We now require long-term clinical trials first to assess the therapeutic potential of ET receptor antagonists compared to placebo in patients with chronic heart failure, and then, if successful, we need to see direct comparison studies with selective ETA and non-selective receptor antagonists. Only then will we know if endothelin antagonists have fulfilled their potential as new therapeutic agents for the treatment of chronic heart failure.