Document Detail


Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment.
MedLine Citation:
PMID:  16301359     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Chronic heart failure (CHF) is a major cause of morbidity and mortality that requires a novel approach to therapy. Perhexiline is an antianginal drug that augments glucose metabolism by blocking muscle mitochondrial free fatty acid uptake, thereby increasing metabolic efficiency. We assessed the effects of perhexiline treatment in CHF patients.
METHODS AND RESULTS: In a double-blind fashion, we randomly assigned patients with optimally medicated CHF to either perhexiline (n=28) or placebo (n=28). The primary end point was peak exercise oxygen consumption (VO2max), an important prognostic marker. In addition, the effect of perhexiline on myocardial function and quality of life was assessed. Quantitative stress echocardiography with tissue Doppler measurements was used to assess regional myocardial function in patients with ischemic CHF. 31P magnetic resonance spectroscopy was used to assess the effect of perhexiline on skeletal muscle energetics in patients with nonischemic CHF. Treatment with perhexiline led to significant improvements in VO2max (16.1+/-0.6 to 18.8+/-1.1 mL . kg(-1) . min(-1); P<0.001), quality of life (Minnesota score reduction from 45+/-5 to 34+/-5; P=0.04), and left ventricular ejection fraction (24+/-1% to 34+/-2%; P<0.001). Perhexiline treatment also increased resting and peak dobutamine stress regional myocardial function (by 15% and 24%, respectively) and normalized skeletal muscle phosphocreatine recovery after exercise. There were no adverse effects during the treatment period.
CONCLUSIONS: In patients with CHF, metabolic modulation with perhexiline improved VO2max, left ventricular ejection fraction, symptoms, resting and peak stress myocardial function, and skeletal muscle energetics. Perhexiline may therefore represent a novel treatment for CHF with a good safety profile, provided that the dosage is adjusted according to plasma levels.
Authors:
Leong Lee; Ross Campbell; Michaela Scheuermann-Freestone; Rachel Taylor; Prasad Gunaruwan; Lynne Williams; Houman Ashrafian; John Horowitz; Alan G Fraser; Kieran Clarke; Michael Frenneaux
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  112     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-11-22     Completed Date:  2006-02-27     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3280-8     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Aged
Cardiovascular Agents / administration & dosage*,  adverse effects
Chronic Disease
Echocardiography, Stress
Fatty Acids / metabolism
Female
Glucose / metabolism
Heart Failure / drug therapy*,  metabolism*,  ultrasonography
Humans
Male
Middle Aged
Myocardial Ischemia / drug therapy,  metabolism
Myocardium / metabolism*
Oxygen Consumption / drug effects
Perhexiline / administration & dosage*,  adverse effects
Quality of Life
Stroke Volume / drug effects
Treatment Outcome
Grant Support
ID/Acronym/Agency:
PS/02/002/14893//British Heart Foundation; RG/07/004/22659//British Heart Foundation
Chemical
Reg. No./Substance:
0/Cardiovascular Agents; 0/Fatty Acids; IY9XDZ35W2/Glucose; KU65374X44/Perhexiline
Comments/Corrections
Comment In:
Circulation. 2005 Nov 22;112(21):3218-21   [PMID:  16301353 ]

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


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