Relation between impaired antiplatelet response to clopidogrel and possible pleiotropic effects

Abstract

The study was designed to determine whether impaired antiplatelet response to clopidogrel but not to aspirin may be responsible for loss of pleiotropic effects of the drug. Study included 34 consecutive patients with STEMI undergoing primary percutaneous coronary intervention (PCI) with stent implantation treated with aspirin (loading dose 300 mg followed by 75 mg/day) and clopidogrel (loading dose 600 mg followed by 75 mg/day). On the basis of Platelet Function Analyzer (PFA)-100 test which measured closure times (CT) in test with collagen/epinephrine (CEPI-CT) or collagen/adenosine diphosphate (CADP-CT) patients were stratified after 7 days from admission as full aspirin or clopidogrel responders (CEPI-CT or CADP-CT = 300 sec., respectively) and non-full aspirin or clopidogrel responders (CEPI-CT or CADP-CT < 300 sec., respectively). High sensitivity C-reactive protein (hs-CRP) was measured at baseline and after 7 days of treatment. All patients received comparable statin treatment. Median and interquartile ranges (IQR) of hs-CRP increased significantly from 2.5 mg/L (0.4-44.8) at baseline to 8.05 mg/L (1.4-33.9) at day 7 (P = .002) in non-full clopidogrel responders subgroup and only slightly in the full clopidogrel responders subgroup (2.45 mg/L, IQR 0.4-48.3 vs. 4.2 mg/L, IQR 1.9-17.5) (P = .3) remaining within reference intervals. On the contrary median and IQR of hs-CRP increased significantly in both non-full aspirin responders (2.4 mg/L, IQR 1.3-3.3 vs. 5.8 mg/L, IQR 3.2-14.8, P = .01) and full aspirin responders (2.9 mg/L, IQR 2.0-3.7 vs. 5.6 mg/L, IQR 4.3-12.9, P = .04). Impaired antiplatelet response to clopidogrel but not to aspirin may contribute to smaller anti-inflammatory response in patients with ST-elevation myocardial infarction.