title: Clinic and ambulatory blood pressure lowering effect of aliskiren/amlodipine/hydrochlorothiazide combination in patients with moderate-to-severe hypertension:  a randomized active-controlled trial.
abstract: OBJECTIVE
  To evaluate the clinic and ambulatory blood pressure (BP)-lowering efficacy and safety of an aliskiren/amlodipine/hydrochlorothiazide (HCT) triple combination compared with the component dual combinations, in patients with moderate-to-severe hypertension.
  
  
  METHODS
  This 8-week, double-blind, randomized, active-controlled study, after 1-4 weeks single-blind placebo run-in period, randomized 1191 patients to receive once-daily aliskiren/amlodipine 150/5 mg (n = 287), aliskiren/HCT 150/12.5 mg (n = 298), amlodipine/HCT 5/12.5 mg (n = 296), or aliskiren/amlodipine/HCT 150/5/12.5 mg (up-titrated from aliskiren/HCT 150/12.5 mg after initial 3 days) (n = 310) for 4 weeks, followed by forced titration to double the initial dose for the next 4 weeks.
  
  
  RESULTS
  Baseline mean sitting SBP and DBP (msSBP/msDBP) was comparable among treatment groups. The aliskiren/amlodipine/HCT combination resulted in significant least squares mean reduction in msSBP/msDBP from baseline to endpoints (week 4, -30.7/-15.9  mmHg; week 8, -37.9/-20.6  mmHg), superior (P < 0.001) to each of the dual combinations. The triple combination was associated with -27.8  mmHg reduction in msSBP at week 2, significantly better than the dual combinations (P < 0.05). Significantly greater mean SBP/DBP-lowering effect for triple vs. dual combinations was also demonstrated through 24-h, daytime, and night-time ambulatory BP measurements. Significantly greater (P < 0.001) BP control (msSBP/msDBP < 140/90  mmHg) was achieved with triple combination in patients with moderate-to-severe (62.3%) and severe (57.5%) hypertension.
  
  
  CONCLUSIONS
  Aliskiren/amlodipine/HCT at 150/5/12.5 mg (week 4) and 300/10/25 mg (week 8) provided statistically superior reductions in msSBP/msDBP and greater BP control rates vs. the dual combinations, and was well tolerated. The improved efficacy of BP reduction was evident within 2 weeks of initiating triple therapy even at low dose.
authors: Unité de Recherche Sur L'hypertension, Centre Hospitalier Universitaire de Québec (CHUL), Quebec, Quebec, Canada. ylacourcierehta@hotmail.ca
authors: Yves
authors: Y
authors: Lacourcière
authors: Stefano
authors: S
authors: Taddei
authors: George
authors: G
authors: Konis
authors: Hui
authors: H
authors: Fang
authors: Thomas
authors: T
authors: Severin
authors: Jack
authors: J
authors: Zhang
mesh_terms: D000368:Aged; D000577:Amides / Q000008:administration & dosage / Q000627:therapeutic use; D017311:Amlodipine / Q000008:administration & dosage / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005650:Fumarates / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012720:Severity of Illness Index; D016037:Single-Blind Method
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D010919:Placebos; D006852:Hydrochlorothiazide; D017311:Amlodipine; C446481:aliskiren