Aliskiren versus ramipril in hypertension.
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.
Verdecchia
Paolo
P
Department of Cardiology, Clinical Research Unit 'Preventive Cardiology', Hospital Santa Maria della Misericordia, 06156 Perugia, Italy. verdec@tin.it
Angeli
Fabio
F
Mazzotta
Giovanni
G
Martire
Paola
P
Garofoli
Marta
M
Gentile
Giorgio
G
Reboldi
Gianpaolo
G
D000375:Aging; D000577:Amides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003925:Diabetic Angiopathies / Q000188:drug therapy; D005650:Fumarates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006207:Half-Life; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D017257:Ramipril / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000187:drug effects
D000577:Amides; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D005650:Fumarates; D000804:Angiotensin II; C446481:aliskiren; C052549:ramiprilat; D017257:Ramipril