title: Influence of diabetes on efficacy of aliskiren, losartan or both on left ventricular mass regression.
abstract: HYPOTHESIS/ INTRODUCTION: We investigated whether diabetes modified the effectiveness of renin-angiotensin-aldosterone system (RAAS) inhibition on left ventricular hypertrophy (LVH) regression in hypertensive patients in the Aliskiren in Left Ventricular Hypertrophy (ALLAY) trial.
  
  
  METHODS
  Participants (n=465) with LVH and a BMI > 25 kg/m(2) were randomized to aliskiren 300mg, losartan 100mg or both daily for 36 weeks, and LVH regression was assessed by cardiac magnetic resonance imaging. Renin concentration, plasma renin activity and aldosterone were assessed in a subset of patients.
  
  
  RESULTS
  Patients with diabetes mellitus (DM) (n=111, 24%) were older (61±9 vs. 58±11 years, p=0.03), had higher BMI (32.2±4.2 vs. 30.7 ± 4 kg/m(2), p=0.004), higher systolic blood pressure (148±14 vs. 145±14mmHg, p=0.03) and lower eGFR (79±16 vs. 84±16ml/min, p=0.03) at baseline. Combination therapy with aliskiren plus losartan was associated with greater LVH reduction than losartan alone in patients with DM (p=0.01), but not in patients without DM (p=0.91; unadjusted interaction p=0.06; adjusted p = 0.038). In a subset of 138 participants, plasma aldosterone was reduced to a greater extent in patients with DM (p-interaction = 0.004).
  
  
  CONCLUSIONS
  Patients with DM and LVH may derive differential benefit with dual RAAS inhibition with a combination of aliskiren and losartan compared with losartan alone with respect to LVH reduction. Whether these findings will result in improved outcomes will be further explored in larger studies.
authors.affiliation: University of Wisconsin School of Pharmacy, Madison, WI 53705-2222, USA. ovardeny@pharmacy.wisc.edu
authors.forename: Orly
authors.initials: O
authors.lastname: Vardeny
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Pouleur
authors.forename: Madoka
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Evan
authors.initials: E
authors.lastname: Appelbaum
authors.forename: Anil
authors.initials: A
authors.lastname: Verma
authors.forename: Margaret
authors.initials: M
authors.lastname: Prescott
authors.forename: Beverly
authors.initials: B
authors.lastname: Smith
authors.forename: Bjorn
authors.initials: B
authors.lastname: Dahlof
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000577:Amides / Q000494:pharmacology / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D048909:Diabetes Complications / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005650:Fumarates / Q000494:pharmacology / Q000627:therapeutic use*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000187:drug effects; D012083:Renin / Q000097:blood; D016896:Treatment Outcome
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D015415:Biomarkers; D005650:Fumarates; D000450:Aldosterone; C446481:aliskiren; D012083:Renin; D019808:Losartan