Journal article
Pharmacogenetic interactions between angiotensin-converting enzyme inhibitor therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure
Journal of the American College of Cardiology, Vol.44(10), pp.2019-2026
11/16/2004
DOI: 10.1016/j.jacc.2004.08.048
PMID: 15542286
Abstract
We evaluated the interaction of angiotensin-converting enzyme (ACE) inhibitor therapy with the effect of the ACE D/I polymorphism on heart failure survival.
The ACE deletion allele, ACE-D, is associated with increased ACE activity. The utilization of ACE genotyping to predict the impact of ACE inhibitor dose has not been previously evaluated.
We prospectively studied 479 subjects with systolic dysfunction (left ventricular ejection fraction 0.25 ± 0.08). Subjects were divided on the basis of ACE inhibitor therapy into low dose (≤50% of target dose, n = 227), standard (high) dose (>50%, n = 201), or those receiving angiotensin receptor antagonists (n = 51). Patients were genotyped for the ACE D/I polymorphism, followed to the end point of death or cardiac transplantation, and transplant-free survival compared by genotype.
The ACE-D allele was associated with an increased risk of events (p = 0.026). In analysis by ACE inhibitor dose, this effect was primarily in the low-dose group (1-year percent event-free survival: II/ID/DD = 86/77/71,2-year = 79/66/59, p = 0.032). In the standard-dose group, the impact was markedly diminished (1-year: II/ID/DD = 91/81/80, 2-year: 77/70/71, p = 0.64). The impact of beta-blockers and high dose ACE inhibitors was greatest in subjects with the ACE DD genotype (p = 0.001) and was less apparent with the II and ID genotypes (p = 0.38).
Higher doses of ACE inhibitors diminished the impact of the ACE-D allele, and the benefits of beta-blockers and high-dose ACE inhibitors appeared maximal for DD patients. Determination of ACE genotype may help target therapy for patients with heart failure.
Details
- Title: Subtitle
- Pharmacogenetic interactions between angiotensin-converting enzyme inhibitor therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure
- Creators
- Dennis M McNamara - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PennsylvaniaRichard Holubkov - Department of Family and Preventive Medicine, School of Medicine, University of Utah, Salt Lake City, UtahLisa Postava - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PennsylvaniaKaren Janosko - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PennsylvaniaGuy A MacGowan - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PennsylvaniaMichael Mathier - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PennsylvaniaSrinivas Murali - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PennsylvaniaArthur M Feldman - Department of Medicine, Thomas Jefferson Medical Center, Philadelphia, PennsylvaniaBarry London - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
- Resource Type
- Journal article
- Publication Details
- Journal of the American College of Cardiology, Vol.44(10), pp.2019-2026
- DOI
- 10.1016/j.jacc.2004.08.048
- PMID
- 15542286
- NLM abbreviation
- J Am Coll Cardiol
- ISSN
- 0735-1097
- eISSN
- 1558-3597
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 11/16/2004
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984025324502771
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