Current concepts: renin inhibition in the treatment of hypertension.
The development of aliskiren, the first orally effective renin inhibitor, utilized molecular modeling based upon X-ray crystallographic analysis of renin's active site to design a potent, low molecular weight renin inhibitor with improved bioavailability (approximately 2.6%). In patients with hypertension, dose-dependent BP reduction occurs with aliskiren 75-300 mg once daily; at these doses, the safety and tolerability profile is comparable to placebo. In direct comparison studies, BP reduction with aliskiren is equivalent to commonly used antihypertensive agents including diuretics, ACE inhibitors, and ARBs. Persistent BP reduction and prolonged suppression of plasma renin activity (PRA) is observed after aliskiren withdrawal. Aliskiren suppresses PRA when given either as monotherapy or in combination with other agents. When added to an ARB, aliskiren blocks compensatory RAS activation and produces significant additional BP reduction. In patients with diabetic nephropathy, addition of aliskiren to losartan, 100 mg resulted in a 20% greater reduction in proteinuria. Ongoing studies evaluating the long-term renal protective effects of aliskiren and its effects on ventricular remodeling are currently planned or underway.
Gradman
Alan H
AH
Division of Cardiovascular Diseases, The Western Pennsylvania Hospital, 4800 Friendship Avenue, North Tower, Suite 3411, Pittsburgh, PA, USA. gradmanmd@aol.com
Pinto
Rekha
R
Kad
Rishi
R
D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D005650:Fumarates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D012083:Renin / Q000494:pharmacology*; D000092502:Renin Inhibitors
D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren