title: High-dose atorvastatin enhances the decline in inflammatory markers in patients with acute coronary syndromes in the MIRACL study.
abstract: BACKGROUND
  Inflammation promotes acute coronary syndromes and ensuing clinical complications. Although statins reduce inflammatory markers in asymptomatic adults or in patients with stable angina, the effect of statins on the markedly heightened inflammation in patients with acute coronary syndromes is unknown.
  
  
  RESULTS
  We measured C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) in 2402 subjects enrolled the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study. Subjects with unstable angina or non-Q-wave myocardial infarction were randomized to atorvastatin 80 mg/d or placebo within 24 to 96 hours of hospital admission and treated for 16 weeks. The effect of treatment on inflammatory markers was assessed by ANCOVA after adjustment for presenting syndrome, country, and initial level of marker. All 3 markers were markedly elevated at randomization and declined over the 16 weeks in both treatment groups. Compared with placebo, atorvastatin significantly reduced CRP, -83% (95% CI, -84%, -81%) versus -74% (95% CI, -75%, -71%) (P<0.0001) and SAA, -80% (95% CI, -82%, -78%) versus -77% (-79%, -75%) (P=0.0006) but not IL-6, -55% (95% CI, -57%, -53%) versus -53% (95% CI, -55%, -51%) (P=0.3). Reductions in CRP and SAA were observed in patients with unstable angina and non-Q-wave myocardial infarction, with initial LDL cholesterol <3.2 or > or =3.2 mmol/L (125 mg/dL), age > or =65 or <65 years, and in men and women. By 16 weeks, CRP was 34% lower with atorvastatin than with placebo.
  
  
  CONCLUSIONS
  High-dose atorvastatin potentiated the decline in inflammation in patients with acute coronary syndromes. This supports the value of early statin therapy in these patients.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St, Boston, Mass 02115, USA. skinlay@partners.org
authors.forename: Scott
authors.initials: S
authors.lastname: Kinlay
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Schwartz
authors.forename: Anders G
authors.initials: AG
authors.lastname: Olsson
authors.forename: Nader
authors.initials: N
authors.lastname: Rifai
authors.forename: Sally J
authors.initials: SJ
authors.lastname: Leslie
authors.forename: William J
authors.initials: WJ
authors.lastname: Sasiela
authors.forename: Michael
authors.initials: M
authors.lastname: Szarek
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.forename: Peter
authors.initials: P
authors.lastname: Ganz
mesh_terms: D000208:Acute Disease; D000368:Aged; D000789:Angina, Unstable / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D001053:Apolipoproteins / Q000097:blood; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D000685:Serum Amyloid A Protein; D013577:Syndrome; D014336:Troponin / Q000097:blood
chemical_list: D001053:Apolipoproteins; D015415:Biomarkers; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D011758:Pyrroles; D000685:Serum Amyloid A Protein; D014336:Troponin; D002097:C-Reactive Protein; D000069059:Atorvastatin