title: Double-blind, randomized, placebo-controlled study of high-dose HMG CoA reductase inhibitor therapy on ventricular remodeling, pro-inflammatory cytokines and neurohormonal parameters in patients with chronic systolic heart failure.
abstract: BACKGROUND
  Statins decrease mortality in patients with coronary artery disease. However, chronic heart failure (CHF) patients were often excluded in such trials. Statins possess pharmacologic properties (independent of cholesterol lowering) that may be beneficial on ventricular remodeling in such patients.
  
  
  RESULTS
  We conducted a 6-month randomized placebo (PBO)-controlled study of rosuvastatin (ROS) in patients with systolic (left ventricular ejection fraction [LVEF] <40%) CHF of ischemic or nonischemic etiology. The primary end point was change in LVEF by radionuclide ventriculogram. Secondary end points included change in echocardiographic parameters, neurohormonal and inflammatory markers, Packer composite score, death, and heart failure hospitalization. Patients were well matched for baseline values. Compared with PBO (n = 46), ROS patients (n = 40) had a decrease in low-density lipoprotein cholesterol (PBO +3, ROS -54%, P < .001). There was no significant change in LVEF by radionuclide ventriculogram (PBO +5.3, ROS +3.2%), fractional shortening by echocardiographic (PBO +2.7, ROS +1.8%), left ventricular end-diastolic diameter (PBO -1.7, ROS +0.8 mm), left ventricular end-systolic diameter (PBO -1.9, ROS +0.1 mm). Plasma norepinephrine, endothelin-1, brain natriuretic peptide, hsCRP, tumor necrosis factor-alpha and interleukin-6, patient global assessment, Packer composite, death/heart failure hospitalization, and adverse events were similar between PBO and ROS.
  
  
  CONCLUSIONS
  Despite being safe and effective at decreasing plasma cholesterol, high-dose ROS did not beneficially alter parameters of LV remodeling. Reasons for absence of benefit are uncertain, but may include patient population studied, high dose of ROS used or high use of effective background CHF medications.
authors.affiliation: Monash University, Alfred Hospital, Melbourne, Victoria, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.forename: Emma
authors.initials: E
authors.lastname: Ashton
authors.forename: Christopher
authors.initials: C
authors.lastname: Reid
authors.forename: Victor
authors.initials: V
authors.lastname: Kalff
authors.forename: Jim
authors.initials: J
authors.lastname: Rogers
authors.forename: John
authors.initials: J
authors.lastname: Amarena
authors.forename: Bhuwan
authors.initials: B
authors.lastname: Singh
authors.forename: Andrew
authors.initials: A
authors.lastname: Tonkin
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005464:Fluorobenzenes / Q000494:pharmacology / Q000627:therapeutic use*; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000097:blood; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D013599:Systole; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D016207:Cytokines; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018377:Neurotransmitter Agents; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium