title: Effect of the direct renin inhibitor aliskiren on left ventricular remodelling following myocardial infarction with systolic dysfunction.
abstract: OBJECTIVE
  Direct renin inhibitors provide an alternative approach to inhibiting the renin-angiotensin-aldosterone system (RAAS) at the most proximal, specific, and rate-limiting step. We tested the hypothesis that direct renin inhibition would attenuate left ventricular remodelling in patients following acute myocardial infarction receiving stable, individually optimized therapy, including another inhibitor of the RAAS.
  
  
  RESULTS
  We randomly assigned 820 patients between ∼2 and 8 weeks following acute myocardial infarction, with the left ventricular ejection fraction (LVEF) ≤45%, and regional wall motion abnormalities (≥20% akinetic area), to receive aliskiren (n = 423), titrated to 300 mg, or matched placebo (n = 397), added to the standard therapy. All patients were required to be on a stable dose of an ACE-inhibitor or ARB, and beta-blocker unless contraindicated or not tolerated. Echocardiograms were obtained at baseline, and following 26-36 weeks of treatment. The primary endpoint was change in left ventricular end-systolic volume from baseline to 36 weeks, and was evaluable in 329 patients in the placebo group and 343 patients in the aliskiren group. We observed no difference in the primary endpoint of end-systolic volume change between patients randomized to aliskiren (-4.4 ± 16.8 mL) or placebo (-3.5 ± 16.3 mL), or in secondary measures of end-diastolic volume, or LVEF. We also observed no differences in a composite endpoint of cardiovascular death, hospitalization for heart failure, or reduction in LVEF >6 points. There were more investigator reported adverse events in the aliskiren group, including hypotension, increases in creatinine and hyperkalaemia.
  
  
  CONCLUSIONS
  Adding the direct renin inhibitor aliskiren to the standard therapy, including an inhibitor of the RAAS, in high-risk post-MI patients did not result in further attenuation of left ventricular remodelling, and was associated with more adverse effects. These findings do not suggest that dual RAAS blockade with aliskiren would provide additional benefit in these high-risk post-MI patients.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA. ssolomon@rics.bwh.harvard.edu
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Shin
authors.forename: Amil
authors.initials: A
authors.lastname: Shah
authors.forename: Hicham
authors.initials: H
authors.lastname: Skali
authors.forename: Akshay
authors.initials: A
authors.lastname: Desai
authors.forename: Lars
authors.initials: L
authors.lastname: Kober
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.forename: Jean L
authors.initials: JL
authors.lastname: Rouleau
authors.forename: Roxzana Y
authors.initials: RY
authors.lastname: Kelly
authors.forename: Allen
authors.initials: A
authors.lastname: Hester
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
mesh_terms: D000368:Aged; D000577:Amides / Q000627:therapeutic use*; D001794:Blood Pressure; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D016757:Death, Sudden, Cardiac / Q000209:etiology; D005260:Female; D005650:Fumarates / Q000627:therapeutic use*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D012008:Recurrence; D013599:Systole; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy*; D020257:Ventricular Remodeling / Q000187:drug effects*; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D002316:Cardiotonic Agents; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren