Document Detail


Antianginal efficacy of omapatrilat in patients with chronic angina pectoris.
MedLine Citation:
PMID:  15904630     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Angiotensin-converting enzyme inhibition is not an effective antianginal therapy. Experimental data suggest that broader vasopeptidase inhibition may decrease the magnitude of demand-induced myocardial ischemia. A randomized, double-blind, placebo controlled parallel study evaluated omapatrilat, an inhibitor of angiotensin-converting enzyme and neutral endopeptidase. The primary objective was to compare maximum duration of exercise at peak plasma concentrations. Exercise treadmill studies were performed in 348 patients who had chronic angina at baseline and after 4 weeks of therapy with 80 mg/day omapatrilat or placebo. Safety data were collected and reported for all patients. Treadmill exercise duration at peak was significantly prolonged in the omapatrilat group compared with the placebo group (76.6 +/- 84.2 vs 28.7 +/- 82.2 seconds difference from baseline, p <0.001). Similar statistically significant increases were seen in time to onset of level III/IV angina and time to onset of >/=0.1-mV ST-segment depression (p <0.001). The significant improvements in exercise duration and measurements of myocardial ischemia were not sustained 20 to 28 hours after dosing. Omapatrilat was generally well tolerated in this predominantly normotensive population. The incidence of serious adverse events was 5.2% in the 2 groups. Thus, omapatrilat, an investigational vasopeptidase inhibitor, is effective in prolonging exercise duration and parameters of demand-induced myocardial ischemia in patients who have chronic angina at peak concentrations. The data confirm the proof of principle that broader vasopeptidase inhibition beyond angiotensin-converting enzyme inhibition is required to alleviate symptoms of chronic angina.
Authors:
Bernard R Chaitman; Alla Y Ivleva; Marek Ujda; Jacque H F Lenis; Csaba Toth; David M Stieber; Leonardo H Reisin; Andreas M Pangerl; Julie B Friedman; John H Lawrence
Publication Detail:
Type:  Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of cardiology     Volume:  95     ISSN:  0002-9149     ISO Abbreviation:  Am. J. Cardiol.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-05-20     Completed Date:  2005-07-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0207277     Medline TA:  Am J Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1283-9     Citation Subset:  AIM; IM    
Affiliation:
Saint Louis University School of Medicine, St. Louis, Missouri 63117, USA. chaitman@slu.edu
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MeSH Terms
Descriptor/Qualifier:
Angina Pectoris / drug therapy*
Angiotensin II / analogs & derivatives*,  blood
Angiotensin III / blood
Angiotensin-Converting Enzyme Inhibitors / administration & dosage,  adverse effects,  therapeutic use*
Cardiovascular Agents / administration & dosage,  adverse effects,  therapeutic use*
Chronic Disease
Double-Blind Method
Exercise Tolerance / drug effects*
Female
Humans
Male
Middle Aged
Neprilysin / antagonists & inhibitors*
Pyridines / administration & dosage,  adverse effects,  therapeutic use*
Thiazepines / administration & dosage,  adverse effects,  therapeutic use*
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Cardiovascular Agents; 0/Pyridines; 0/Thiazepines; 0/omapatrilat; 11128-99-7/Angiotensin II; 12687-51-3/Angiotensin III; 23025-68-5/angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; EC 3.4.24.11/Neprilysin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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