Blood pressure lowering in essential hypertension with an oral renin inhibitor, aliskiren.
Inhibition of the first and rate-limiting step of the renin-angiotensin system has long been an elusive therapeutic goal. Aliskiren, the first known representative of a new class of completely nonpeptide, orally active, renin inhibitors, has been shown to inhibit the production of angiotensin I and II in healthy volunteers and to reduce blood pressure (BP) in sodium-depleted marmosets. The aim of this randomized, double-blind, active comparator trial study was to assess the BP-lowering efficacy and safety of aliskiren. Two hundred twenty-six patients, 21 to 70 years of age, with mild to moderate hypertension, were randomly assigned to receive 37.5 mg, 75 mg, 150 mg, or 300 mg aliskiren or 100 mg losartan daily for 4 weeks. Dose-dependent reductions in daytime ambulatory systolic pressure (mean change, mm Hg [SD of change]; -0.4 [11.7], -5.3 [11.3], -8.0 [11.0], and -11.0 [11.0], P=0.0002) and in plasma renin activity (median change % [interquartile range]; -55 [-64, -11], -60 [-82, -46], -77 [-86, -72], and -83 [-92, -71], P=0.0008) were observed with 37.5, 75, 150, and 300 mg aliskiren. The change in daytime systolic pressure with 100 mg losartan (-10.9 [13.8]) was not significantly different from the changes seen with 75, 150, and 300 mg aliskiren. Aliskiren was well tolerated at all doses studied. This study demonstrates that aliskiren, through inhibition of renin, is an effective and safe orally active BP-lowering agent. Whether renin inhibition results in protection from heart attack, stroke, and nephropathy, similar to angiotensin-converting enzyme inhibition and angiotensin receptor blockade, needs to be researched.
Stanton
Alice
A
Blood Pressure Unit, Beaumont Hospital, Dublin, Ireland. astanton@rcsi.ie
Jensen
Chris
C
Nussberger
Juerg
J
O'Brien
Eoin
E
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000577:Amides; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005650:Fumarates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D012083:Renin / Q000097:blood; D000092502:Renin Inhibitors
D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D019808:Losartan; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren