PMID- 10968433
OWN - NLM
STAT- MEDLINE
DCOM- 20000920
LR  - 20220310
IS  - 0140-6736 (Print)
IS  - 0140-6736 (Linking)
VI  - 356
IP  - 9230
DP  - 2000 Aug 19
TI  - Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise 
      tolerance and morbidity in patients with heart failure: IMPRESS randomised trial.
PG  - 615-20
AB  - 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.
FAU - Rouleau, J L
AU  - Rouleau JL
AD  - Division of Cardiology, Toronto General Hospital, University of Toronto, ON, 
      Canada. jrouleau@torhosp.toronto.on.ca
FAU - Pfeffer, M A
AU  - Pfeffer MA
FAU - Stewart, D J
AU  - Stewart DJ
FAU - Isaac, D
AU  - Isaac D
FAU - Sestier, F
AU  - Sestier F
FAU - Kerut, E K
AU  - Kerut EK
FAU - Porter, C B
AU  - Porter CB
FAU - Proulx, G
AU  - Proulx G
FAU - Qian, C
AU  - Qian C
FAU - Block, A J
AU  - Block AJ
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - England
TA  - Lancet
JT  - Lancet (London, England)
JID - 2985213R
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Endothelin-1)
RN  - 0 (Pyridines)
RN  - 0 (Thiazepines)
RN  - 11128-99-7 (Angiotensin II)
RN  - 36NLI90E7T (omapatrilat)
RN  - 85637-73-6 (Atrial Natriuretic Factor)
RN  - E7199S1YWR (Lisinopril)
RN  - EC 3.4.24.11 (Neprilysin)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
EIN - Lancet 2000 Nov 18;356(9243):1774
CIN - Lancet. 2000 Aug 19;356(9230):608-9. PMID: 10968427
CIN - Lancet. 2000 Oct 28;356(9240):1526. PMID: 11081561
CIN - Rev Cardiovasc Med. 2001 Spring;2(2):104. PMID: 12506942
MH  - Angiotensin II/blood
MH  - Angiotensin-Converting Enzyme Inhibitors/adverse effects/*therapeutic use
MH  - Atrial Natriuretic Factor/blood
MH  - Double-Blind Method
MH  - Endothelin-1/blood
MH  - Exercise Tolerance/*drug effects
MH  - Female
MH  - Heart Failure/blood/diagnostic imaging/*drug therapy/mortality
MH  - Humans
MH  - Lisinopril/adverse effects/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Neprilysin/*antagonists & inhibitors
MH  - Norepinephrine/blood
MH  - Prospective Studies
MH  - Pyridines/adverse effects/*therapeutic use
MH  - Radionuclide Ventriculography
MH  - Severity of Illness Index
MH  - Survival Rate
MH  - Thiazepines/adverse effects/*therapeutic use
MH  - Treatment Outcome
EDAT- 2000/09/01 11:00
MHDA- 2000/09/23 11:01
CRDT- 2000/09/01 11:00
PHST- 2000/09/01 11:00 [pubmed]
PHST- 2000/09/23 11:01 [medline]
PHST- 2000/09/01 11:00 [entrez]
AID - S0140673600026027 [pii]
AID - 10.1016/s0140-6736(00)02602-7 [doi]
PST - ppublish
SO  - Lancet. 2000 Aug 19;356(9230):615-20. doi: 10.1016/s0140-6736(00)02602-7.