Document Detail

Aliskiren versus ramipril in hypertension.
MedLine Citation:
PMID:  20418269     Owner:  NLM     Status:  MEDLINE    
Aliskiren is an orally active direct renin inhibitor which inhibits the synthesis of angiotensin I by linking to active renin on a deep cleft of its molecular structure, the site of hydrolysis of the Leu10-Val11 bond of angiotensinogen. At variance with angiotensin-converting enzyme (ACE) inhibitors, aliskiren eliminates the main substrate for the 'escape' phenomenon (synthesis of angiotensin II from angiotensin I through alternative enzymatic pathways). The possibility that the antihypertensive effect of aliskiren differs from that of ACE inhibitors needs to be proved in specifically designed clinical trials. Over the past 2 years, three studies have been published which directly compared aliskiren with ramipril, in patients with hypertension. We made a pooled analysis of these studies. In order to avoid interference with additional drugs, analysis was restricted to trial periods when the two drugs were given as monotherapy. In each individual study, systolic blood pressure (BP) was slightly lower with aliskiren. Overall, systolic BP was lower with aliskiren than with ramipril (weighted mean difference between the treatments 1.84 mmHg; fixed effect model; p < 0.0001; and 1.87 mmHg; random effect model; p = 0.0055). The standardized mean difference between the treatments was 2.58 (fixed effect model; p < 0.0001) and 2.92 (random effect model; p = 0.0017) in favor of aliskiren. Compared with ramipril, aliskiren may have induced a more complete 'upstream' inhibition of the renin-angiotensin-aldosterone system, with consequent greater suppression of angiotensin II. Another potential explanation may be the longer terminal elimination halflife of aliskiren (about 40 hours) compared with ramiprilat (13-17 hours). These data provide further evidence that aliskiren monotherapy provides a sustained BP reduction over the 24 hours.
Paolo Verdecchia; Fabio Angeli; Giovanni Mazzotta; Paola Martire; Marta Garofoli; Giorgio Gentile; Gianpaolo Reboldi
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2010-04-23
Journal Detail:
Title:  Therapeutic advances in cardiovascular disease     Volume:  4     ISSN:  1753-9455     ISO Abbreviation:  Ther Adv Cardiovasc Dis     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-27     Completed Date:  2010-09-09     Revised Date:  2011-03-11    
Medline Journal Info:
Nlm Unique ID:  101316343     Medline TA:  Ther Adv Cardiovasc Dis     Country:  England    
Other Details:
Languages:  eng     Pagination:  193-200     Citation Subset:  IM    
Department of Cardiology, Clinical Research Unit 'Preventive Cardiology', Hospital Santa Maria della Misericordia, 06156 Perugia, Italy.
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MeSH Terms
Amides / pharmacokinetics,  therapeutic use*
Angiotensin II / antagonists & inhibitors
Angiotensin-Converting Enzyme Inhibitors / pharmacokinetics,  therapeutic use*
Antihypertensive Agents / pharmacokinetics,  therapeutic use*
Blood Pressure / drug effects
Diabetic Angiopathies / drug therapy
Fumarates / pharmacokinetics,  therapeutic use*
Hypertension / drug therapy*
Ramipril / analogs & derivatives,  pharmacokinetics,  therapeutic use*
Renin-Angiotensin System / drug effects
Reg. No./Substance:
0/Amides; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/Fumarates; 0/aliskiren; 11128-99-7/Angiotensin II; 87269-97-4/ramiprilat; 87333-19-5/Ramipril
Erratum In:
Ther Adv Cardiovasc Dis. 2010 Aug;4(4):277

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

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