Relation between impaired antiplatelet response to clopidogrel and possible pleiotropic effects.

Background: 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.

Methods: 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.

Results: 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).

Conclusions: Impaired antiplatelet response to clopidogrel but not to aspirin may contribute to smaller anti-inflammatory response in patients with ST-elevation myocardial infarction.