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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


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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