Circulation. 2003;108:1560-1566
Published online before print September 15, 2003, doi: 10.1161/01.CIR.0000091404.09558.AF
Published online before print September 15, 2003, doi: 10.1161/01.CIR.0000091404.09558.AF
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(Circulation. 2003;108:1560.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
High-Dose Atorvastatin Enhances the Decline in Inflammatory Markers in Patients With Acute Coronary Syndromes in the MIRACL Study
From the Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass (S.K., P.L., P.G.); Cardiology Division, Veterans Affairs Medical Center and University of Colorado Health Sciences Center, Denver (G.G.S.); Faculty of Health Sciences, University of Linköping, Linköping, Sweden (A.G.O.); Children’s’ Hospital Boston and Harvard Medical School, Boston, Mass (N.R.); and Pfizer Pharmaceuticals Group, New York, NY (S.J.L., W.J.S., M.S.).
Correspondence to Scott Kinlay, MBBS, PhD, FRACP, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail skinlay{at}partners.org
Received February 24, 2003; de novo received May 6, 2003; revision received June 13, 2003; accepted June 16, 2003.
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.
Methods and 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 
3.2 mmol/L (125 mg/dL), age 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.
Key Words: inflammation • myocardial infarction • angina
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