title: Long-term safety, tolerability and efficacy of combination therapy with aliskiren and amlodipine in patients with hypertension.
abstract: OBJECTIVE
  Most patients with hypertension require antihypertensive combination therapy to achieve BP control. This study investigated the safety and efficacy of the direct renin inhibitor aliskiren combined with the calcium channel blocker amlodipine.
  
  
  METHODS
  Overall, 556 patients with hypertension (msDBP > or =95-<110 mmHg) received open-label aliskiren/amlodipine 150/5 mg for 2 weeks, followed by forced titration to aliskiren/amlodipine 300/10 mg for 52 weeks. Add-on hydrochlorothiazide (HCT) was permitted from week 10 to achieve BP control (<140/90 mmHg). The primary objective of the study was to evaluate the long-term safety and tolerability of aliskiren/amlodipine combination therapy; the BP-lowering efficacy of the combination was also assessed (week 54 endpoint; last observation carried forward).
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT00402103.
  
  
  RESULTS
  In total, 452 patients completed 54 weeks' treatment with aliskiren/amlodipine 300/10 mg, with or without add-on HCT. The most frequently reported adverse events (AEs) were peripheral edema, upper respiratory tract infection, headache and bronchitis. Peripheral edema (the most common AE), occurred in 22.7% of treated patients, and was generally mild or moderate in intensity and transient in nature. Few patients exhibited laboratory abnormalities. Aliskiren/amlodipine combination therapy provided a mean BP reduction from baseline to week 54 of 24.2/15.5 mmHg; 74.3% of patients achieved BP control. In the subgroup of patients with stage 2 hypertension (baseline msSBP > or =160 mmHg and/or msDBP > or =100 mmHg), the mean BP reduction at week 54 was 29.1/17.1 mmHg, and 67.0% of patients achieved BP control.
  
  
  CONCLUSIONS
  In this open-label study, aliskiren/amlodipine 300/10 mg combination therapy, with or without add-on HCT, effectively reduced BP, particularly in patients with stage 2 hypertension. The most common AE was peripheral edema, consistent with the known AE profile of high-dose (10 mg) amlodipine. Further studies comparing the aliskiren/amlodipine combination with the component monotherapies and other antihypertensive combinations are warranted.
authors.affiliation: Piedmont Medical Research Associates, Winston-Salem, NC 27103, USA. TWLittlejohn@pmg-research.com
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Littlejohn
authors.forename: Peter
authors.initials: P
authors.lastname: Trenkwalder
authors.forename: Geert
authors.initials: G
authors.lastname: Hollanders
authors.forename: Yanxing
authors.initials: Y
authors.lastname: Zhao
authors.forename: Weichi
authors.initials: W
authors.lastname: Liao
mesh_terms: D000328:Adult; D000368:Aged; D000577:Amides / Q000009:adverse effects / Q000627:therapeutic use*; D017311:Amlodipine / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003971:Diastole / Q000187:drug effects; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005260:Female; D005650:Fumarates / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D012449:Safety; D013599:Systole / Q000187:drug effects
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D017311:Amlodipine; C446481:aliskiren