title: Effect of aliskiren on progression of coronary disease in patients with prehypertension: the AQUARIUS randomized clinical trial.
abstract: OBJECTIVE
  Blood pressure reduction and renin-angiotensin-aldosterone system inhibition are targets for treatment of atherosclerosis. The effect of renin inhibition on coronary disease progression has not been investigated.
  
  
  OBJECTIVE
  To determine the effects of renin inhibition with aliskiren on progression of coronary atherosclerosis.
  
  
  METHODS
  A double-blind, randomized, multicenter trial (Aliskiren Quantitative Atherosclerosis Regression Intravascular Ultrasound Study) comparing aliskiren with placebo in 613 participants with coronary artery disease, systolic blood pressure between 125 and 139 mm Hg (prehypertension range), and 2 additional cardiovascular risk factors conducted at 103 academic and community hospitals in Europe, Australia, and North and South America (enrollment from March 2009 to February 2011; end of follow-up: January 31, 2013).
  
  
  METHODS
  Participants underwent coronary intravascular ultrasound (IVUS) imaging and were randomized to receive 300 mg of aliskiren (n = 305) or placebo (n = 308) taken orally daily for 104 weeks. Disease progression was measured by repeat IVUS examination after at least 72 weeks of treatment.
  
  
  METHODS
  The primary efficacy parameter was the change in percent atheroma volume (PAV) from baseline to study completion. Secondary efficacy parameters included the change in normalized total atheroma volume (TAV) and the percentage of participants with atheroma regression. Safety and tolerability were also assessed.
  
  
  RESULTS
  Evaluable imaging data were available at baseline and follow-up for 458 participants (74.7%). The primary IVUS efficacy parameter, PAV, did not differ between participants treated with aliskiren (-0.33%; 95% CI, -0.68% to 0.02%) and placebo (0.11%; 95% CI, -0.24% to 0.45%) (between-group difference, -0.43% [95% CI, -0.92% to 0.05%]; P = .08). The secondary IVUS efficacy parameter, TAV, did not differ between participants treated with aliskiren (-4.1 mm3; 95% CI, -6.27 to -1.94 mm3) and placebo (-2.1 mm3; 95% CI, -4.21 to 0.07 mm3) (between-group difference, -2.04 mm3 [95% CI, -5.03 to 0.95 mm3]; P = .18). There were no significant differences in the proportion of participants who demonstrated regression of PAV (56.9% vs 48.9%; P = .08) and TAV (64.4% vs 57.5%; P = .13) in the aliskiren and placebo groups, respectively.
  
  
  CONCLUSIONS
  Among participants with prehypertension and coronary artery disease, the use of aliskiren compared with placebo did not result in improvement or slowing of progression of coronary atherosclerosis. These findings do not support the use of aliskiren for regression or prevention of progression of coronary atherosclerosis.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00853827.
authors.affiliation: South Australian Health and Medical Research Institute, Adelaide, Australia. stephen.nicholls@sahmri.com
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
authors.forename: George L
authors.initials: GL
authors.lastname: Bakris
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Venu
authors.initials: V
authors.lastname: Menon
authors.forename: Bryan
authors.initials: B
authors.lastname: Williams
authors.forename: Juergen
authors.initials: J
authors.lastname: Armbrecht
authors.forename: Patrick
authors.initials: P
authors.lastname: Brunel
authors.forename: Maria
authors.initials: M
authors.lastname: Nicolaides
authors.forename: Amy
authors.initials: A
authors.lastname: Hsu
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.forename: Hui
authors.initials: H
authors.lastname: Fang
authors.forename: Rishi
authors.initials: R
authors.lastname: Puri
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Uno
authors.forename: Yu
authors.initials: Y
authors.lastname: Kataoka
authors.forename: Dianna
authors.initials: D
authors.lastname: Bash
authors.forename: Steven E
authors.initials: SE
authors.lastname: Nissen
mesh_terms: D000368:Aged; D000577:Amides / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000473:pathology; D003331:Coronary Vessels / Q000000981:diagnostic imaging; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005650:Fumarates / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058246:Prehypertension; D012084:Renin-Angiotensin System; D012307:Risk Factors; D018084:Ultrasonography, Interventional; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren