Relation between impaired antiplatelet response to clopidogrel and possible pleiotropic effects Lukasz A. Malek Æ Marcin Grabowski Æ Mateusz Spiewak Æ Krzysztof J. Filipiak Æ Monika Szpotanska Æ Tomasz Imiela Æ Zenon Huczek Æ Dagna Bobilewicz Æ Grzegorz Opolski Published online: 3 April 2007 Ó Springer Science+Business Media, LLC 2007 Abstract Background The study was designed to determine whe- ther 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 inter- vention (PCI) with stent implantation treated with aspirin (loading dose 300 mg followed by 75 mg/day) and clopi- dogrel (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/epineph- rine (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 clopi- dogrel 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 clopido- grel but not to aspirin may contribute to smaller anti- inflammatory response in patients with ST-elevation myocardial infarction. Keywords Platelets Á Clopidogrel Á Drug response Á Pleiotropic effects Introduction Antiplatelet therapy is a cornerstone of cardiovascular medicine. It influences the success of percutaneous coro- nary intervention (PCI) in patients with acute coronary syndromes [1]. On the other hand interindividual vari- ability in platelet response to either aspirin or clopidogrel has become an emerging clinical entity [2–6]. Several studies disclosed that impaired response to antiplatelet drugs is responsible for persistent platelet activation in patients undergoing PCI with stenting [2–6]. In several studies clopidogrel has been shown to have anti-inflammatory effect measured by decrease in biomar- ker levels such as high sensitivity C-reactive protein (hs-CRP) [7, 8]. In other study withdrawal of clopidogrel was associated not only with prothrombotic but also with proinflammatory effects measured by increase in CRP levels [9]. On the other hand hs-CRP has been established as effective and independent marker in predicting the risk for adverse outcomes in patients with acute coronary L. A. Malek (&) Á M. Grabowski Á M. Spiewak Á K. J. Filipiak Á M. Szpotanska Á T. Imiela Á Z. Huczek Á G. Opolski 1st Department of Cardiology, Medical University of Warsaw, 1a Banacha Str, Warsaw 02-097, Poland e-mail: lamalek@amwaw.edu.pl D. Bobilewicz Department of Laboratory Diagnostics, Medical University of Warsaw, Warsaw, Poland 123 J Thromb Thrombolysis (2007) 24:301–305 DOI 10.1007/s11239-007-0026-8