Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure: IMPRESS randomised trial

Lancet. 2000 Aug 19;356(9230):615-20. doi: 10.1016/s0140-6736(00)02602-7.


Background: We aimed to assess in patients with congestive heart failure whether dual inhibition of neutral endopeptidase and angiotensin-converting enzyme (ACE) with the vasopeptidase inhibitor omapatrilat is better than ACE inhibition alone with lisinopril on functional capacity and clinical outcome.

Methods: We did a prospective, randomised, double-blind, parallel trial of 573 patients with New York Heart Association (NYHA) class II-IV congestive heart failure, left-ventricular ejection fraction of 40% or less, and receiving an ACE inhibitor. Patients were randomly assigned omapatrilat at a daily target dose of 40 mg (n=289) or lisinopril at a daily target dose of 20 mg (n=284) for 24 weeks. The primary endpoint was improvement in maximum exercise treadmill test (ETT) at week 12. Secondary endpoints included death and comorbid events indicative of worsening heart failure.

Findings: Week 12 ETT increased similarly in the omapatrilat and lisinopril groups (24 vs 31 s, p=0.45). The two drugs were fairly well tolerated, but there were fewer cardiovascular-system serious adverse events in the omapatrilat group than in the lisinopril group (20 [7%] vs 34 [12%], p=0.04). There was a suggestive trend in favour of omapatrilat on the combined endpoint of death or admission for worsening heart failure (p=0.052; hazard ratio 0.53 [95% CI 0.27-1.02]) and a significant benefit of omapatrilat in the composite of death, admission, or discontinuation of study treatment for worsening heart failure (p=0.035; 0.52 [0.28-0.96]). Omapatrilat improved NYHA class more than lisinopril in patients who had NYHA class III and IV (p=0.035), but not if patients with NYHA class II were included.

Interpretation: Our findings suggest that omapatrilat could have some advantages over lisinopril in the treatment of patients with congestive heart failure. Thus use of vasopeptidase inhibitors could constitute a potentially important treatment for further improving the prognosis and well being of patients with this disorder.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Angiotensin II / blood
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Atrial Natriuretic Factor / blood
  • Double-Blind Method
  • Endothelin-1 / blood
  • Exercise Tolerance / drug effects*
  • Female
  • Heart Failure / blood
  • Heart Failure / diagnostic imaging
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Humans
  • Lisinopril / adverse effects
  • Lisinopril / therapeutic use*
  • Male
  • Middle Aged
  • Neprilysin / antagonists & inhibitors*
  • Norepinephrine / blood
  • Prospective Studies
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Radionuclide Ventriculography
  • Severity of Illness Index
  • Survival Rate
  • Thiazepines / adverse effects
  • Thiazepines / therapeutic use*
  • Treatment Outcome


  • Angiotensin-Converting Enzyme Inhibitors
  • Endothelin-1
  • Pyridines
  • Thiazepines
  • Angiotensin II
  • omapatrilat
  • Atrial Natriuretic Factor
  • Lisinopril
  • Neprilysin
  • Norepinephrine