Document Detail


The anti-ischemic mechanism of action of ranolazine in stable ischemic heart disease.
MedLine Citation:
PMID:  20828645     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: The purpose of this explanatory analysis was to investigate the relationship between ST-segment depression and the rate-pressure product (RPP) during exercise to determine whether ranolazine's mechanism of action was related to a reduction in myocardial oxygen demand or preservation of myocardial oxygen supply.
BACKGROUND: In patients with stable ischemic heart disease, ranolazine increases exercise duration and reduces maximal ST-segment depression while exerting minimal effects on heart rate and blood pressure, although its mechanism of action during exercise has not been investigated.
METHODS: Patients with stable ischemic heart disease (n = 191) were randomly allocated to a 4-period, double-blind, balanced Latin square crossover study to receive placebo, and ranolazine 500, 1,000, and 1,500 mg twice daily (bid) for 1 week each. Exercise treadmill tests were performed at baseline and at the end of each treatment period. The RPP and ST-segment depression were assessed before starting exercise, at each stage of exercise, and at maximal exercise.
RESULTS: Compared with placebo, ranolazine produced a dose-dependent reduction in ST-segment depression that became more marked as exercise-induced ischemia became more pronounced, associated with clinically minor decreases in heart rate and blood pressure. At 12-min exercise, the amount of ST-segment depression compared with placebo and controlled for RPP was reduced by 22.3% on ranolazine 500 mg bid (p = 0.137), by 35.4% on 1,000 mg bid (p = 0.005), and by 45.8% on 1,500 mg bid (p < 0.001).
CONCLUSIONS: The progressive magnitude of ischemia reduction on ranolazine was proportionally more substantial than the minor reductions in heart rate or RPP, suggesting that ranolazine's beneficial mechanism of action is most likely primarily due to an improvement in regional coronary blood flow in areas of myocardial ischemia.
Authors:
Peter H Stone; Bernard R Chaitman; Karen Stocke; Junko Sano; Arthur DeVault; Gary G Koch
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Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  56     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-10     Completed Date:  2010-10-29     Revised Date:  2011-10-05    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  934-42     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Affiliation:
Cardiovascular Division, Brigham & Women’s Hospital, Boston, Massachusetts 02115, USA. pstone@partners.org.
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MeSH Terms
Descriptor/Qualifier:
Acetanilides / administration & dosage*
Adult
Aged
Aged, 80 and over
Blood Pressure
Cross-Over Studies
Dose-Response Relationship, Drug
Double-Blind Method
Electrocardiography
Enzyme Inhibitors / administration & dosage*
Exercise Test
Female
Heart Rate
Humans
Male
Middle Aged
Myocardial Ischemia / drug therapy*
Piperazines / administration & dosage*
Time Factors
Chemical
Reg. No./Substance:
0/Acetanilides; 0/Enzyme Inhibitors; 0/Piperazines; 110445-25-5/ranolazine
Comments/Corrections
Comment In:
J Am Coll Cardiol. 2011 Aug 30;58(10):1083; author reply 1083-4   [PMID:  21867850 ]
J Am Coll Cardiol. 2010 Sep 14;56(12):943-5   [PMID:  20828646 ]

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


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