title: Effects of aliskiren in diabetic and non-diabetic patients with coronary artery disease: Insights from AQUARIUS.
abstract: BACKGROUND
  Aliskiren previously was found to have potentially harmful effects in diabetic individuals prescribed concomitant angiotensin converting enzyme inhibitors (ACEI) or angiotenisn receptor antagonists (ARB). We explored potential effects of aliskiren on coronary atheroma progression and major adverse cardiovascular events (MACE: death/non-fatal MI/non-fatal stroke/hospitalization for heart failure/hospitalization for ACS/arterial revascularization) in patients with and without diabetes mellitus (DM).
  
  
  METHODS
  AQUARIUS employed serial intravascular ultrasound measures of coronary atheroma volume in coronary artery disease patients randomized to receive daily aliskiren 300 mg or placebo for 104 weeks. This post hoc analysis compared changes in plaque volume [percent atheroma volume (PAV) and total atheroma volume (TAV)] and MACE in patients with (n = 115) and without (n = 343) DM stratified by treatment allocation.
  
  
  RESULTS
  In multivariable propensity-weighted analyses, which included controlling for baseline and concomitant ACEI/ARB therapy and duration of aliskiren therapy, aliskiren-treated non-DM patients demonstrated the greatest PAV and TAV regression, whereas aliskiren-treated DM patients demonstrated the greatest TAV progression and greater PAV. Aliskiren-treated non-DM patients appeared at significantly lower risk of MACE compared with their aliskiren-treated DM counterparts [HR 95% CI 0.28 (0.10, 0.80)]. Statistical interactions were noted between DM status and treatment allocation for both changes in PAV (p < 0.001), TAV (p = 0.010) and MACE (p = 0.057).
  
  
  CONCLUSIONS
  Aliskiren appears to be relatively anti-atherosclerotic in non-diabetic patients. Due to the limited number MACE and low numbers of diabetic patients in AQUARIUS, the pro-atherosclerotic effects of aliskiren in this population are inconclusive, and these results should be thus considered hypothesis generating. Further outcome studies are required in non-diabetic patients to confirm the possible favorable effects of aliskiren.
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research (C5R), Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA; Department of Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Rishi
authors.initials: R
authors.lastname: Puri
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research (C5R), Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Nissen
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research (C5R), Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Venu
authors.initials: V
authors.lastname: Menon
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research (C5R), Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Shao
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research (C5R), Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Hsu
authors.affiliation: Department of Medicine, ASH Comprehensive Hypertension Center, University of Chicago Medicine, Chicago, IL, USA.
authors.forename: George L
authors.initials: GL
authors.lastname: Bakris
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.affiliation: National Institute of Health Research, University College London Hospitals Biomedical Research Centre, London, England, UK.
authors.forename: Bryan
authors.initials: B
authors.lastname: Williams
authors.affiliation: Novartis Pharmaceuticals, Basel, Switzerland.
authors.forename: Juergen
authors.initials: J
authors.lastname: Armbrecht
authors.affiliation: Novartis Pharmaceuticals, Basel, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Brunel
authors.affiliation: South Australian Health and Medical Research Institute, Adelaide, Australia.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kataoka
authors.affiliation: Department of Medicine, University of Adelaide, Adelaide, Australia; South Australian Health and Medical Research Institute, Adelaide, Australia. Electronic address: stephen.nicholls@sahmri.com.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
mesh_terms: D000368:Aged; D000577:Amides / Q000008:administration & dosage* / Q000009:adverse effects; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016009:Chi-Square Distribution; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects*; D003925:Diabetic Angiopathies / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005650:Fumarates / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000401:mortality; D058226:Plaque, Atherosclerotic; D058246:Prehypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D057216:Propensity Score; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional
chemical_list: D000577:Amides; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D005650:Fumarates; C446481:aliskiren
keywords: Aliskiren; Atherosclerosis; IVUS; Renin inhibition: diabetes mellitus