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Comparison of the dual receptor endothelin antagonist enrasentan with enalapril in asymptomatic left ventricular systolic dysfunction: a cardiovascular magnetic resonance study
  1. S K Prasad1,
  2. H J Dargie2,
  3. G C Smith1,
  4. M M Barlow2,
  5. F Grothues1,
  6. B A Groenning2,
  7. J G F Cleland3,
  8. D J Pennell1
  1. 1Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, London, UK
  2. 2Western Infirmary, Glasgow, UK
  3. 3University of Hull, Hull, UK
  1. Correspondence to:
    Dr Sanjay K Prasad
    Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK; s.prasad{at}rbh.nthames.nhs.uk

Abstract

Objective: To compare the effect of the dual endothelin A/B receptor antagonist enrasentan with enalapril on left ventricular (LV) remodelling.

Methods: Multicentre, randomised, double blind, parallel group study of 72 asymptomatic patients with LV dysfunction. Patients received enrasentan (60–90 mg/day) or enalapril (10–20 mg/day). The primary end point was the change in LV end diastolic volume index (EDVI) after six months’ treatment.

Results: LV EDVI increased with enrasentan but decreased with enalapril (3.9 (1.8) v −3.4 (1.4) ml/m2, p  =  0.001). Enrasentan increased resting cardiac index compared with enalapril (0.11 (0.07) v −0.10 (0.07) l/m2, p  =  0.04), as well as LV mass index (0.67 (1.6) v −3.6 (1.6) g/m2, p  =  0.04). Other variables were comparable between groups. Enalapril lowered brain natriuretic peptide more than enrasentan (–19.3 (9.4) v –5.8 (6.9) pg/ml, p  =  0.005). Noradrenaline (norepinephrine) (p  =  0.02) increased more with enrasentan than with enalapril. Enrasentan was associated with more serious adverse events compared with enalapril (six (16.7%) patients v one (2.8%), p  =  0.02); the rate of progression of heart failure did not differ.

Conclusion: In asymptomatic patients with LV dysfunction, LV EDVI increased over six months with enrasentan compared with enalapril treatment, with adverse neurohormonal effects. This suggests that enrasentan at a dose of 60–90 mg/day over six months causes adverse ventricular remodelling despite an increase in the resting cardiac index.

  • ACE, angiotensin converting enzyme
  • BNP, brain natriuretic peptide
  • CARMEN, carvedilol ACE inhibitor remodelling mild CHF evaluation
  • CMR, cardiovascular magnetic resonance
  • EARTH, endothelin A receptor antagonist trial in heart failure trial
  • EDVI, end diastolic volume index
  • EF, ejection fraction
  • ENABLE, endothelin antagonist bosentan for lowering events
  • ENCOR, enrasentan cooperative randomised evaluation
  • HF, heart failure
  • LV, left ventricular
  • NYHA, New York Heart Association
  • REACH-1, randomised endothelin antagonism in chronic heart failure with bosentan
  • left ventricle
  • endothelin antagonist
  • remodelling
  • enrasentan
  • cardiovascular magnetic resonance

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Footnotes

  • Published Online First 9 December 2005

  • This study was sponsored by SmithKline Beecham (now part of Glaxo SmithKline). Part of the findings of this paper were presented in abstract form at the AHA Annual Scientific meeting in 2002.

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