Randomized comparison of the effects of ASA plus clopidogrel versus ASA alone on early platelet activation in acute coronary syndromes with elevated high-sensitivity C-reactive protein and soluble CD40 ligand levels

Background: High-sensitivity C-reactive protein (hsCRP) and soluble cluster of differentiation 40 ligand (sCD40L) have been established as effective markers of inflammation in predicting the risk for adverse outcomes in patients with acute coronary syndromes (ACSs). Activated platelets secrete certain inflammatory mediators such as P-selectin and sCD40L, which play a role in the pathogenesis of ACSs. Although acetylsalicylic acid (ASA) has been found to be an effective treatment of ACSs, the addition of clopidogrel bisulfate has been found to further improve clinical outcomes as a result of additional antiplatelet and anti-inflammatory action. Few data exist concerning the effects of dual antiplatelet therapy on these markers in patients with ACSs. Objective: The aim of this study was to assess the effectiveness and clinical significance of clopidogrel administration in patients with ACSs without ST segment elevation treated with ASA. Methods: This randomized, single-blind, controlled trial was conducted at the First Department of Cardiology, Hippokration Hospital, Athens, Greece. Inpatients aged >= 21 years with ACSs without ST segment elevation were randomly assigned to 1 of 2 groups: ASA 325 mg/d for 1 week, followed by ASA (100 mg/d) plus clopidogrel (300-mg loading dose followed by 100 mg/d) for 36 weeks (ASA + Clop group) or ASA alone (325 mg/d for 1 week, followed by 75 mg/d for 36 weeks) (ASA group). Levels of serum sCD40L, hsCRP, and P-selectin were determined on admission and at 8 hours, 48 hours, and 6 days of treatment. By means of clinical follow-up, Kaplan-Meier free-of-major adverse cardiovascular events (MACES) plots were used to assess the prevalence of MACES, including cardiovascular-related death, in patients with and without high levels of hsCRP (>= 3 mg/L) and sCD40L (>= 5 ug/L) for 52 weeks. Results: A total of 86 patients were enrolled (71 men, 15 women; mean [SD] age, 68 [3] years; mean [SD] weight, 86 [18] kg; white race, 86 [100%]; 43 patients per group). Both groups had similar initial clinical characteristics and P-selectin levels. Baseline hsCRP and sCD40L levels were correlated with baseline P-selectin levels (hsCRP, r(2) = 0.099 [P < 0.003]; sCD40L, r(2) = 0.122 [P < 0.001]). In the ASA group, patients with high serum levels of hsCRP and sCD40L had significantly increased mean (SD) P-selectin levels at 8 hours compared with baseline (P = 0.032). In the ASA + Clop group, patients with high hsCRP and sCD40L did not have any significant increases in P-selectin. The ASA + Clop subgroup with high levels of hsCRP and sCD40L had a significantly lower prevalence of MACES compared with that in the ASA group (P = 0.048). MACES included ACS requiring hospital readmission in 12 (28%) and 18 (42%) patients in the ASA + Clop and ASA groups, respectively; and cardiovascular-related death in 1 (2%) patient in each subgroup. Conclusions: The results of this small study suggest that early activation of platelets, as measured using P-selectin levels, was effectively inhibited by the addition of clopidogrel to a regimen of ASA in the subgroup of patients with ACSs and intense activation of platelets (defined as high hsCRP and sCD40L levels). In patients without high hsCRP and sCD40L levels, the addition of clopidogrel did not have a significant effect on P-selectin levels.