Published online before print July 19, 2004, doi: 10.1161/01.CIR.0000136588.62638.5E
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(Circulation. 2004;110:386-391.)
© 2004 American Heart Association, Inc.
Original Articles |
Effect of Atorvastatin on Risk of Recurrent Cardiovascular Events After an Acute Coronary Syndrome Associated With High Soluble CD40 Ligand in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study
From the Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass (S.K., P.G., P.L.); Cardiology Division, Veterans Affairs Medical Center and University of Colorado Health Sciences Center, Denver, Colo (G.G.S.); Faculty of Health Sciences, University of Linköping, Linköping, Sweden (A.G.O.); Childrens Hospital Boston and Harvard Medical School, Boston, Mass (N.R.); and Pfizer Pharmaceuticals Group, New York, NY (M.S., W.J.S.).
Correspondence to Peter Libby, MD, Leducq Center for Cardiovascular Research, Brigham and Women’s Hospital, 221 Longwood Ave, Boston, MA 02115. E-mail plibby{at}rics.bwh.harvard.edu
Received October 27, 2003; de novo received February 13, 2004; revision received April 20, 2004; accepted April 22, 2004.
Background— Patients with acute coronary syndromes have elevated plasma levels of the proinflammatory, prothrombotic cytokine CD40 ligand (sCD40L). Statins inhibit CD40L signaling in vitro, but there are no prospective studies of statins and sCD40L in acute coronary syndromes.
Methods and Results— We measured sCD40L in subjects with an acute coronary syndrome enrolled in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study. Subjects were randomized in this double-blind trial to atorvastatin 80 mg/d or placebo for 16 weeks. Plasma CD40L was measured from 2908 (94%) of 3086 subjects at baseline and 2352 (76%) at 16 weeks. Odds ratios (ORs) and 95% CIs from logistic regression models assessed the risk of recurrent cardiovascular events over 16 weeks (death, nonfatal myocardial infarction, cardiac arrest, and worsening angina requiring rehospitalization) in the placebo group from baseline sCD40L and the effect of atorvastatin on the risk associated with CD40L in all subjects. The effects of atorvastatin on plasma concentrations of CD40L were assessed by Wilcoxon tests. There was a threshold effect, with only high sCD40L (>90th centile) being a risk factor for a recurrent cardiovascular event (OR 1.86, 95% CI 1.25 to 2.77). This risk was abolished by atorvastatin (OR 1.09, 95% CI 0.69 to 1.76), which reduced the risk by 48%. Atorvastatin had only a modest effect on sCD40L (P=0.08).
Conclusions— In patients with acute coronary syndromes, atorvastatin abrogated the risk of recurrent cardiovascular events associated with high sCD40L. Early statin therapy after acute coronary syndromes counters the risk associated with elevated sCD40L.
Key Words: inflammation • thrombosis • statins • risk • trials
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