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.