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European Journal of Heart Failure 2003 5(4):415-417; doi:10.1016/S1388-9842(03)00007-2
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© 2003 European Society of Cardiology

Endothelin receptor antagonists in heart failure—a refutation of a bold conjecture?

Lukas E. Spieker* and Thomas F. Lüscher

Cardiovascular Center, Division of Cardiology, University Hospital, Cardiovascular Research, Institute of Physiology and Clinical Research Center InterCorNet, CH-8091 Zurich, Switzerland

* E-mail address: cardiotfl@gmx.ch

The first 10% of the full text of this article appears below.


   1. Introduction
 
The potent vasoconstrictor endothelin (ET)-1 essentially contributes to increased vascular resistance in heart failure [1]. Indeed, circulating ET-1 levels are substantially elevated and correlate both with the hemodynamic severity and NYHA class of the patients. Circulating levels of the ET-1 precursor, big ET-1, are strong independent predictors of death. ET receptor antagonists impressively improve hemodynamics without causing neurohormonal activation in patients with chronic heart failure. However, the recent ENABLE trial showed neutral effects in terms of mortality and symptoms.

Science is driven by conjectures and refutations [2]. Is this a refutation of the concept? Do we have to quit this promising class of drugs?


   2. Physiologic actions of endothelin-1
 
Activation of specific ETA receptors on vascular smooth muscle cells causes vasoconstriction and cell proliferation [3]. Arterial smooth muscle cells also express ETB receptors mediating part of the vasoconstriction. In contrast, ETB receptors on endothelial . . . [Full Text of this Article]


   3. Clinical studies with ET antagonists in heart failure
 

   4. What is the problem?
 

   5. Was the concept tested appropriately?
 
5.1. Did we reach the ceiling with neurohumoral blockade in chronic heart failure?
5.2. Different effects in different patients?

   6. Where do we go from here?
 

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