| Disparate results of ACE inhibitor dosage on exercise capacity in heart failure: a reappraisal of vasodilator therapy and study design. | |
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MedLine Citation:
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PMID: 11182188 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Despite manifest benefits of angiotensin converting enzyme (ACE) inhibitors on the prognosis of patients with heart failure, there is a lack of consistency in the results of trials investigating the effects of ACE inhibitors on exercise capacity. The inconsistencies cannot be readily explained by variations in effects on known neurohumoral or conventional haemodynamic factors. Drawing on insights from physiology of pump-load interactions, in a normal circulation there is an optimal extent of systemic vasodilation at which the delivery of hydraulic energy from the cardiac pump is maximal (the 'impedance matchpoint'). In heart failure, the vasoconstrictive effects shift the operating point towards mismatch at higher resistances, and optimal vasodilatory therapy would reshift the operating point to the matchpoint. Excessive dosage, however, would cause overvasodilatation leading to a reduction in cardiac power output and consequently compromising exercise ability. High levels of ACE inhibitors may not therefore improve exercise ability. Another potential reason for the observed inconsistencies is that the often used parallel-group study design (ideal for mortality studies) may not be suitable for investigating drug effects on exercise capacity because dropouts from such studies would introduce occult selection biases, thereby confounding treatment effects. In conclusion, this reappraisal of the conflicting observations reported on ACE inhibitor effects on exercise capacity has highlighted a proposition that there is an optimal dosage of ACE inhibitors which will most enhance exercise capacity, and this will require further well designed cross-over studies to elucidate. |
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Authors:
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S G Williams; G A Cooke; D J Wright; L B Tan |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: International journal of cardiology Volume: 77 ISSN: 0167-5273 ISO Abbreviation: Int. J. Cardiol. Publication Date: 2001 Feb |
Date Detail:
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Created Date: 2001-02-22 Completed Date: 2001-07-12 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8200291 Medline TA: Int J Cardiol Country: Ireland |
Other Details:
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Languages: eng Pagination: 239-45 Citation Subset: IM |
Affiliation:
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Institute for Cardiovascular Research, University of Leeds, Yorkshire Heart Centre, Leeds General Infirmary, LS1 3EX, Leeds, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin-Converting Enzyme Inhibitors
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administration & dosage* Cilazapril / administration & dosage Enalapril / administration & dosage Exercise Tolerance / drug effects* Heart Failure / drug therapy*, physiopathology* Hemodynamics Humans Lisinopril / administration & dosage Prognosis Research Design Vasodilator Agents / pharmacology, therapeutic use |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin-Converting Enzyme Inhibitors; 0/Vasodilator Agents; 75847-73-3/Enalapril; 83915-83-7/Lisinopril; 92077-78-6/Cilazapril |
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