Study Question: Patients with acute coronary syndrome (ACS) have elevated plasma levels of the proinflammatory, prothrombotic cytokine CD40 ligand (sCD40L). The present analysis examined the relationship between sCD40L and the risk of recurrent cardiovascular events soon after an ACS in the MIRACL study and tested whether the clinical benefit from statin therapy was related to a reduction in proinflammatory and prothrombotic stimuli associated with sCD40L.Methods: The investigators measured sCD40L in subjects with an ACS enrolled in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study. Subjects were randomized in this double-blind trial either to atorvastatin 80 mg/d or placebo for 16 weeks.Results: Plasma CD40L was measured from 2908 (94%) of 3086 subjects at baseline and 2352 (76%) subjects 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 1.25-2.77). This risk was abolished by atorvastatin (OR 1.09, 95% CI 0.69-1.76), which reduced the risk by 48%. Atorvastatin had only a modest effect on sCD40L (p=0.08).Conclusions: The investigators state that, in patients with ACS, atorvastatin abrogated the risk of recurrent cardiovascular events associated with high sCD40L.Perspective: Patients presenting with ACS with highly elevated sCD40L have a higher risk of recurrent coronary events. In this setting, intensive statin therapy may reduce the risk of recurrent events associated with high sCD40L levels without affecting plasma concentrations of this cytokine. The present study points to anti-inflammatory and antithrombotic actions of statins as an additional mechanism of benefit after ACSs. DM