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Hypertension Management: Rationale for Triple Therapy Based on Mechanisms of Action.
MedLine Citation:
PMID:  23121769     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIMS: An estimated 25% of patients will require 3 antihypertensive agents to achieve blood pressure (BP) control; combination therapy is thus an important strategy in hypertension treatment. This review discusses the triple-therapy combination of an angiotensin receptor blocker (ARB) or direct renin antagonist (DRI) with a calcium channel blocker (CCB) and a diuretic, with a focus on mechanisms of action. DISCUSSION: Multiple physiologic pathways contribute to hypertension. Combining antihypertensive agents not only better targets the underlying pathways, but also helps blunt compensatory responses that may be triggered by single-agent therapy. DRIs and ARBs target the renin-angiotensin-aldosterone system (RAAS) at the initial and final steps, respectively, and both classes lower BP by reducing the effects of angiotensin-2; however, ARBs may trigger a compensatory increase in renin activity. Dihydropyridine CCBs target L-type calcium channels and lower BP through potent vasodilation, but can trigger compensatory activation of the sympathetic nervous system (SNS) and RAAS. Thiazide diuretics lower BP initially through sodium depletion and plasma volume reduction, followed by total peripheral resistance reduction, but can also trigger compensatory activation of the SNS and RAAS. The combination of an agent targeting the RAAS with a CCB and diuretic is rational, and triple combinations of valsartan/amlodipine/hydrochlorothiazide, olmesartan/amlodipine/hydrochlorothiazide, and aliskiren/amlodipine/hydrochlorothiazide have demonstrated greater effectiveness compared with their respective dual-component combinations. In addition, single-pill fixed-dose combinations can address barriers to BP control including clinical inertia and poor adherence. CONCLUSION: Fixed-dose antihypertensive combination products capitalize on complementary mechanisms of action, and have been shown to result in improved BP control. © 2012 Blackwell Publishing Ltd.
Authors:
Joel M Neutel; David H G Smith
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-2
Journal Detail:
Title:  Cardiovascular therapeutics     Volume:  -     ISSN:  1755-5922     ISO Abbreviation:  Cardiovasc Ther     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101319630     Medline TA:  Cardiovasc Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 Blackwell Publishing Ltd.
Affiliation:
Orange County Research Center, Tustin, CA.
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