title: Aliskiren alone or with other antihypertensives in the elderly with borderline and stage 1 hypertension: the APOLLO trial.
abstract: OBJECTIVE
  We studied the unclear question whether blood pressure (BP) lowering reduces cardiovascular disease (CVD) in elderly individuals with systolic BP <160 mm Hg.
  
  
  RESULTS
  We initiated a randomized placebo-controlled stratified 2 × 2 factorial clinical trial evaluating the effects of BP lowering in 11 000 elderly individuals with systolic blood pressure (SBP) between 130 and 159 mm Hg, for 5 years. Following 5-week active run-in, participants were randomized to aliskiren (300 mg) or placebo, and to an additional antihypertensive [hydrochlorothiazide (25 mg) or amlodipine (5 mg)], or their respective placeboes. Study was terminated by sponsor after 1759 subjects (age 72.1 ± 5.2 years, 88% receiving at least one antihypertensive) were randomized and followed for 0.6 year. Study drugs were well tolerated with few serious adverse events during run-in and after randomization, with no significant differences between treatment groups. By design, three levels of BP reductions were achieved, adjusted mean BP reductions of 3.5/1.7 mm Hg (P < 0.001) by aliskiren, 6.8/3.3 mm Hg (P < 0.001) by hydrochlorothiazide or amlodipine, and 10.3/5.0 mm Hg (P < 0.001) by double therapy compared with placebo. Twenty-five major CVD events occurred. Non-significant trends towards fewer CVD events with greater BP reductions are evident: hazard ratios (HR) 0.82 [95% confidence interval (CI): 0.37-1.81] for 3.5 mm Hg SBP reduction; HR 0.45 (95% CI: 0.19-1.04) for 6.8 mm Hg; and HR 0.25 (0.05-1.18) for 10.3 mm Hg reduction for primary composite of CV death, MI, stroke, or significant heart failure.
  
  
  CONCLUSIONS
  Sizeable reductions in BP, with potential for substantial CVD reduction, can be safely achieved using combinations of BP drugs in the elderly with normal high and Stage 1 hypertension.
  
  
  BACKGROUND
  NCT01259297.
authors.affiliation: Population Health Research Institute, McMaster-University-Hamilton Health Sciences, Hamilton, ON, Canada koon.teo@phri.ca teok@mcmaster.ca.
authors.forename: Koon K
authors.initials: KK
authors.lastname: Teo
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Pfeffer
authors.affiliation: Clinica Medica e Dipartimento di Medicina Clinica, Universita Milano-Bicocca, Ospedale San Gerardo di Monza, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancia
authors.affiliation: Population Health Research Institute, McMaster-University-Hamilton Health Sciences, Hamilton, ON, Canada Health Research Board Clinical Research Facility, National University of Ireland Galway, Galway, Ireland.
authors.forename: Martin
authors.initials: M
authors.lastname: O'Donnell
authors.affiliation: Quebec Heart Institute, Hospital Laval, Ste-Foy, QC, Canada.
authors.forename: Gilles
authors.initials: G
authors.lastname: Dagenais
authors.affiliation: Estudios Clinicos Latinoamerica, Rosario, Argentina.
authors.forename: Rafael
authors.initials: R
authors.lastname: Diaz
authors.affiliation: Section of Adult Medicine, College of Medicine, University of the Philippines, Manila, Philippines.
authors.forename: Antonio
authors.initials: A
authors.lastname: Dans
authors.affiliation: National Center for Cardiovascular Diseases, Cardiovascular Institute and FuWai Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Liu
authors.affiliation: Population Health Research Institute, McMaster-University-Hamilton Health Sciences, Hamilton, ON, Canada.
authors.forename: Jackie
authors.initials: J
authors.lastname: Bosch
authors.affiliation: Population Health Research Institute, McMaster-University-Hamilton Health Sciences, Hamilton, ON, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Joseph
authors.affiliation: Population Health Research Institute, McMaster-University-Hamilton Health Sciences, Hamilton, ON, Canada.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Copland
authors.affiliation: Population Health Research Institute, McMaster-University-Hamilton Health Sciences, Hamilton, ON, Canada.
authors.forename: Hyejung
authors.initials: H
authors.lastname: Jung
authors.affiliation: Population Health Research Institute, McMaster-University-Hamilton Health Sciences, Hamilton, ON, Canada.
authors.forename: Janice
authors.initials: J
authors.lastname: Pogue
authors.affiliation: Population Health Research Institute, McMaster-University-Hamilton Health Sciences, Hamilton, ON, Canada.
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
mesh_terms: D000368:Aged; D000577:Amides / Q000008:administration & dosage* / Q000009:adverse effects; D017311:Amlodipine / Q000008:administration & dosage / Q000009:adverse effects; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005650:Fumarates / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000009:adverse effects; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D055118:Medication Adherence; D011188:Potassium / Q000097:blood; D016896:Treatment Outcome
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D006852:Hydrochlorothiazide; D017311:Amlodipine; C446481:aliskiren; D011188:Potassium
keywords: Aliskiren; Clinical trial; Combination therapy; Direct renin inhibitor; Lowering stage 1 hypertension in elderly