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.
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.


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.
Kinlay
Scott
S
Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass 02115, USA.
Schwartz
Gregory G
GG
Olsson
Anders G
AG
Rifai
Nader
N
Sasiela
William J
WJ
Szarek
Michael
M
Ganz
Peter
P
Libby
Peter
P
D000368:Aged; D000787:Angina Pectoris / Q000453:epidemiology / Q000517:prevention & control; D000789:Angina, Unstable / Q000188:drug therapy*; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000097:blood; D000069059:Atorvastatin; D015415:Biomarkers; D023201:CD40 Ligand / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D006323:Heart Arrest / Q000453:epidemiology / Q000517:prevention & control; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D016017:Odds Ratio; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D012008:Recurrence; D012306:Risk; D012995:Solubility; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D015415:Biomarkers; D006538:Heptanoic Acids; D018836:Inflammation Mediators; D011758:Pyrroles; D023201:CD40 Ligand; D000069059:Atorvastatin