title: Safety and tolerability of the direct renin inhibitor aliskiren in combination with angiotensin receptor blockers and thiazide diuretics: a pooled analysis of clinical experience of 12,942 patients.
abstract: Combinations of the direct renin inhibitor aliskiren with angiotensin receptor blockers (ARBs) or diuretics are effective therapeutic regimens for the treatment of hypertension. A large database of safety information has become available during the past several years with aliskiren in combination trials. Data were pooled from 9 short-term (8-week) and 4 longer-term (26- to 52-week) randomized controlled trials of aliskiren in patients with hypertension. Adverse event (AE) rates were assessed for aliskiren combination therapy compared with component monotherapies. In short-term studies, overall AE rates were similar for patients receiving aliskiren/valsartan or aliskiren/diuretic combinations (32.2%-39.8%) and those receiving the component monotherapies (30.0%-39.6%). In longer-term studies, AE rates with aliskiren/losartan (55.5%) and aliskiren/diuretic (45.0%) combination therapy were similar to those with losartan (53.9%) and diuretic (48.9%) alone. Angioedema and hyperkalemia occurred in similar proportions of patients taking combination therapies vs monotherapy. The safety and tolerability profile of aliskiren in combination with the ARBs valsartan or losartan, or diuretic, is similar to aliskiren, ARBs, or diuretics alone.
authors.affiliation: Division of Hypertension and Clinical Pharmacology, Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT 06030-3940, USA. wwhite@nso1.uchc.edu
authors.forename: William B
authors.initials: WB
authors.lastname: White
authors.forename: Robert
authors.initials: R
authors.lastname: Bresalier
authors.forename: Allen P
authors.initials: AP
authors.lastname: Kaplan
authors.forename: Biff F
authors.initials: BF
authors.lastname: Palmer
authors.forename: Robert H
authors.initials: RH
authors.lastname: Riddell
authors.forename: Anastasia
authors.initials: A
authors.lastname: Lesogor
authors.forename: William
authors.initials: W
authors.lastname: Chang
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Keefe
mesh_terms: D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000577:Amides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects*; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005650:Fumarates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012083:Renin / Q000378:metabolism; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000577:Amides; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D005650:Fumarates; D049993:Sodium Chloride Symporter Inhibitors; C446481:aliskiren; D012083:Renin