Why the study?
Do endothelin receptor antagonists improve haemodynamic status and cardiac structure in congestive heart failure and pulmonary hypertension?
Do endothelin receptor antagonists improve haemodynamic status and cardiac structure in congestive heart failure and pulmonary hypertension?
Preclinical evidence strongly supports the potential efficacy of endothelin receptor antagonists for treating congestive heart failure and pulmonary hypertension, paving the way for clinical trials.
ET receptor antagonists should not yet alter clinical practice; leaves open translation of animal benefits to human CHF and PH trials.
Recent clinical and experimental animal trials indicate that endogenously produced endothelin-1 (ET-1) contributes to the abnormal systemic and pulmonary vascular resistance associated with congestive heart failure (CHF) and pulmonary hypertension (PH). In experimental CHF, the chronic blockade of ET-1 actions by ET receptor antagonists clearly improves haemodynamic status, and improves cardiac structure and survival. The latter is based on limited results. In experimental PH there are consistent reports of prevention and reversal of PH, pulmonary vascular remodelling and right ventricular hypertrophy, independent of the inciting mechanisms. These results in experimental animals illustrate the potential efficacy of the ET receptor antagonists in future clinical trials. With five ET receptor antagonists in clinical development, and more on the way, their potential will soon be realised.
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Haleen et al. (1997) studied this question.
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