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(Circulation. 2003;108:2184.)
© 2003 American Heart Association, Inc.

Review: Cardiovascular Drugs

Endothelin Receptor Blockers in Cardiovascular Disease

Stuart Rich, MD; Vallerie V. McLaughlin, MD

From the Rush Heart Institute Center for Pulmonary Heart Disease, Rush Medical College, Chicago, Ill.

Correspondence to Stuart Rich, MD, Center for Pulmonary Heart Disease, Rush-Presbyterian–St Luke’s Medical Center, 1725 W Harrison St, Suite 020, Chicago, IL 60612. E-mail Stuart_Rich{at}rush.edu

Abstract

The endothelin (ET) system is comprised of 4 active ETs, with ET-1 being the predominant isoform in the cardiovascular system. Because of the potent vasoconstricting and mitogenic effects of ET-1 and its involvement in various cardiovascular diseases, blockade of the ET receptor has received considerable attention. ET receptor antagonism has been demonstrated to be beneficial in patients with pulmonary hypertension. The nonselective ET receptor antagonist bosentan improves exercise capacity and increases time to clinical worsening in patients with pulmonary arterial hypertension. The selective ET A receptor antagonist sitaxsentan also improves hemodynamics and exercise capacity in patients with pulmonary arterial hypertension. Results with ET receptor antagonists in congestive heart failure have been disappointing. Although some studies have suggested benefit, larger studies have been neutral. The use of ET receptor antagonists for other conditions has not been fully explored. Future studies with the use of ET receptor antagonists as part of a multidrug regimen are also needed.

Key Words: endothelin • heart failure • pulmonary heart disease

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