PMID- 16740982
OWN - NLM
STAT- MEDLINE
DCOM- 20060705
LR  - 20141120
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 231
IP  - 6
DP  - 2006 Jun
TI  - Clinical trials of endothelin antagonists in heart failure: a question of dose?
PG  - 696-9
AB  - Circulating plasma endothelin (ET)-1 concentrations are substantially elevated, 
      and correlate with the hemodynamic severity and New York Heart Association (NYHA) 
      class, in patients with chronic heart failure (CHF). In early preclinical studies 
      involving different models of experimental heart failure, ET antagonists reduced 
      cardiac pressures, increased cardiac output, and prolonged survival. ET receptor 
      antagonists also impressively improved systemic and pulmonary hemodynamics in 
      patients with CHF, without causing neurohormonal activation. However, recent 
      clinical trials, including the ENABLE (Endothelin Antagonist Bosentan for 
      Lowering Cardiac Events in Heart Failure) and EARTH (Endothelin A Receptor 
      Antagonist Trial in Heart Failure) studies, have shown neutral effects in terms 
      of mortality and symptoms. This paper describes the possible reasons why benefit 
      was not seen in these clinical studies, and suggests what lessons can be learnt 
      from the way the studies were undertaken to apply to future studies.
FAU - Kelland, Nicholas F
AU  - Kelland NF
AD  - Clinical Pharmacology Unit, Centre for Cardiovascular Science, University of 
      Edinburgh, Queen's Medical Research Institute, 3rd Floor East Room E3.22, 47 
      Little France Crescent, Edinburgh, EH16 4TJ, UK.
FAU - Webb, David J
AU  - Webb DJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (Endothelin A Receptor Antagonists)
RN  - 0 (Endothelin-1)
RN  - 0 (Endothelins)
SB  - IM
MH  - Clinical Trials as Topic
MH  - Dose-Response Relationship, Drug
MH  - Endothelin A Receptor Antagonists
MH  - Endothelin-1/*antagonists & inhibitors/pharmacology
MH  - Endothelins/pharmacology
MH  - Heart Failure/*drug therapy
MH  - Humans
MH  - Treatment Outcome
RF  - 30
EDAT- 2006/06/03 09:00
MHDA- 2006/07/06 09:00
CRDT- 2006/06/03 09:00
PHST- 2006/06/03 09:00 [pubmed]
PHST- 2006/07/06 09:00 [medline]
PHST- 2006/06/03 09:00 [entrez]
AID - 231/6/696 [pii]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2006 Jun;231(6):696-9.