Journal of the American Pharmacists Association : JAPhA · 2004
Eplerenone: selective aldosterone antagonism in management of cardiovascular and renal disease.
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Brennan Barbara J, Martin Nancy E
Аннотация
OBJECTIVE: To review the pharmacology, safety, and efficacy data, as well as therapeutic use of eplerenone (Inspra-Pfizer) for management of cardiovascular and renal disease.
DATA SOURCES: A Medline search (January 1980-July 2003) was performed using eplerenone, aldosterone, aldosterone antagonist, spironolactone, and other pertinent terms. Additional articles were identified from bibliographies of retrieved articles.
STUDY SELECTION: All retrievable studies and review articles discussing the pharmacology, safety, and efficacy of eplerenone were evaluated.
DATA EXTRACTION: By the authors.
DATA SYNTHESIS: The detrimental role of the renin-angiotensin-aldosterone system (RAAS) in the pathophysiology of cardiovascular and renal disease has been well documented. Until recently, however, the direct injurious effects of aldosterone on nonclassical tissues such as the brain, heart, and vasculature have been overlooked. Although angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) significantly reduce morbidity and mortality associated with heart disease, preliminary data suggest further benefit with additional aldosterone blockade. The nonselective aldosterone antagonist spironolactone has demonstrated profound morbidity and mortality benefit in heart failure patients, but since its adverse event profile makes it unattractive to patients with milder disease, the need for a selective aldosterone receptor antagonist is evident. Preclinical studies with eplerenone, a recently approved selective aldosterone receptor antagonist, demonstrate a protective effect on nonclassical tissues, thus reducing injury associated with long-term unopposed aldosterone exposure. Early clinical trials with eplerenone have demonstrated additional benefit in hypertension, heart failure, and nephropathy, although long-term morbidity and mortality outcome data in patients with various levels of disease severity are necessary to define the role of eplerenone in current cardiovascular pharmacotherapy.
CONCLUSION: Eplerenone offers a new selective approach to optimizing aldosterone blockade. The availability of additional morbidity and mortality outcome data in various cardiovascular conditions will provide further insights into its role in clinical practice.
DATA SOURCES: A Medline search (January 1980-July 2003) was performed using eplerenone, aldosterone, aldosterone antagonist, spironolactone, and other pertinent terms. Additional articles were identified from bibliographies of retrieved articles.
STUDY SELECTION: All retrievable studies and review articles discussing the pharmacology, safety, and efficacy of eplerenone were evaluated.
DATA EXTRACTION: By the authors.
DATA SYNTHESIS: The detrimental role of the renin-angiotensin-aldosterone system (RAAS) in the pathophysiology of cardiovascular and renal disease has been well documented. Until recently, however, the direct injurious effects of aldosterone on nonclassical tissues such as the brain, heart, and vasculature have been overlooked. Although angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) significantly reduce morbidity and mortality associated with heart disease, preliminary data suggest further benefit with additional aldosterone blockade. The nonselective aldosterone antagonist spironolactone has demonstrated profound morbidity and mortality benefit in heart failure patients, but since its adverse event profile makes it unattractive to patients with milder disease, the need for a selective aldosterone receptor antagonist is evident. Preclinical studies with eplerenone, a recently approved selective aldosterone receptor antagonist, demonstrate a protective effect on nonclassical tissues, thus reducing injury associated with long-term unopposed aldosterone exposure. Early clinical trials with eplerenone have demonstrated additional benefit in hypertension, heart failure, and nephropathy, although long-term morbidity and mortality outcome data in patients with various levels of disease severity are necessary to define the role of eplerenone in current cardiovascular pharmacotherapy.
CONCLUSION: Eplerenone offers a new selective approach to optimizing aldosterone blockade. The availability of additional morbidity and mortality outcome data in various cardiovascular conditions will provide further insights into its role in clinical practice.