Comparison of the effect of valsartan and lisinopril on autonomic nervous system activity in chronic heart failure

Am Heart J. 2003 Nov;146(5):E17. doi: 10.1016/S0002-8703(03)00366-1.


Background: In chronic heart failure (CHF), the derangement of autonomic nervous system activity has a deep impact on the progression of the disease. It has been demonstrated that modulation of the renin-angiotensin aldosterone system (RAAS) increases autonomic control of heart rate and reduces adrenergic activity. We sought to evaluate, in CHF, the different effects of an ACE inhibitor (lisinopril) and of an AT1 receptor antagonist (valsartan) on heart rate variability, baroreflex sensitivity and norepinephrine plasma levels.

Methods: Ninety patients (61 +/- 10 years, 2.3 +/- 0.5, New York Heart Association class) with CHF and left ventricular ejection fraction <40% were randomly assigned in a double-blind fashion to receive lisinopril (uptitrated to 20 mg/d) or valsartan (uptitrated to 160 mg/d) therapy for 16 weeks. Heart rate variability (evaluated by measuring standard deviation of normal R-R intervals on 24-hour ECG recordings), spontaneous baroreflex sensitivity and aldosterone and norepinephrine plasma levels were assessed before and after drug therapy.

Results: There were no significant differences between valsartan and lisinopril in their effects on left ventricular function, arterial pressure, aldosterone plasma levels and autonomic control of heart rate. Both lisinopril and valsartan significantly reduced plasma norepinephrine levels, but the reduction induced by valsartan was significantly greater than that observed for lisinopril (27% vs 6%, P <.05).

Conclusions: This study shows a comparable effect of ACE inhibition (lisinopril) and of AT1 receptor antagonism (valsartan) on cardiac vagal control of heart rate, whereas valsartan has shown a more effective modulation of sympathetic activity measured by plasma norepinephrine levels.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Autonomic Nervous System / drug effects*
  • Disease Progression
  • Double-Blind Method
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology*
  • Heart Rate / drug effects
  • Humans
  • Lisinopril / therapeutic use*
  • Male
  • Middle Aged
  • Norepinephrine / blood
  • Tetrazoles / therapeutic use*
  • Valine / analogs & derivatives
  • Valine / therapeutic use*
  • Valsartan


  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Tetrazoles
  • Valsartan
  • Lisinopril
  • Valine
  • Norepinephrine