Pretreatment with different loading doses of clopidogrel influences P-selectin levels in patients undergoing percutaneous coronary intervention: results from the ARMYDA-2 (antiplatelet therapy for reduction of myocardial damage during angioplasty) SELECT substudy

OBJECTIVES: ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) trial demonstrated improved clinical outcome in patients undergoing percutaneous coronary intervention (PCI) pretreated with 600 vs. 300 mg clopidogrel loading dose. ARMYDA-2 SELECT is a prospectively planned subanalysis to investigate the effects of those different loading regimens on P-selectin levels. METHODS: From the ARMYDA-2 population, we investigated a subgroup of 84 patients (41 randomized to a 600 mg and 43 to a 300 mg clopidogrel loading dose given at a mean time of 6 h before PCI), in whom soluble P-selectin levels were measured at baseline (at the time of clopidogrel administration), immediately after the procedure, and after 8 and 24 h. RESULTS: In the overall study population, a significant decrease of P-selectin levels was observed from baseline to intervention (from 91 ± 10 to 53 ± 15 ng/ml; P < 0.001). Baseline P-selectin levels were similar in the two groups, whereas at the time of intervention they were significantly lower in the high-dose arm (50 ± 13 vs. 58 ± 15 ng/ml; P = 0.048). P-selectin values between the two arms were not different at the subsequent determinations. The lowest procedural P-selectin levels were observed in patients of the 600 mg arm who had no postprocedural increase of troponin-I above normal limits (P ≤ 0.040). CONCLUSION: Pretreatment with clopidogrel before PCI decreases peri-procedural P-selectin levels; moreover, a 600 mg clopidogrel loading dose, compared with the 300 mg regimen, is associated with reduction of peri-procedural myocardial damage and significant attenuation of P-selectin levels at the time of intervention. These results may help in identifying mechanisms underlying clinical benefit of the high clopidogrel load in PCI.