Regular Article High on clopidogrel treatment platelet reactivity is frequent in acute and rare in elective stenting and can be functionally overcome by switch of therapy Sarolta Leé ⁎, Katarina Vargová, István Hizoh, Zsófia Horváth, Petra Gulácsi-Bárdos, Zsófia Sztupinszki, Anna Apró, Andrea Kovács, István Préda, Emese Tóth-Zsámboki, Róbert G. Kiss Medical Center, Hungarian Defence Forces, Department of Cardiology, Budapest, Hungary abstract article info Article history: Received 10 August 2013 Received in revised form 10 November 2013 Accepted 29 November 2013 Available online 6 December 2013 Keywords: Platelet reactivity Light transmission aggregometry Clopidogrel Therapy adjustment Percutaneous coronary intervention Myocardial infarction The benefit of adjusted antiplatelet therapy in patients with myocardial infarction after primary percutaneous coronary intervention is not well elucidated. We aimed to identify patients with high on treatment platelet reac- tivity and to gradually adjust antiplatelet therapy. Materials and Methods: We enrolled 133 acute myocardial infarction and 67 stable angina patients undergoing intracoronary stenting into our study. Maximal aggregation was determined with light transmission aggregometry. Aggregation N 50% induced by 5 μM ADP was indexed with high on-clopidogrel treatment platelet reactivity. In these cases 75 mg clopidogrel was doubled and control test was performed. Patients effectively inhibited with 150 mg clopidogrel were defined as clopidogrel pseudo non-responders. Patients with high plate- let reactivity even on 150 mg clopidogrel were considered as clopidogrel real non-responders and were switched to ticlopidine. Results: Aggregations (5ADP; p = 0.046) and the ratio of real non-responders (p = 0.013) were significantly higher in the myocardial infarction group. Most real non-responders were effectively treated with switch of ther- apy. The ratio of pseudo non-responders also tended to be higher in myocardial infarction. Platelet reactivity remained constant during follow-up; however, a new appearance of high platelet reactivity was observed at 6 and at 12 months. Conclusions: Patients with acute myocardial infarction undergoing percutaneous coronary intervention may ben- efit from prospective platelet function testing, because of higher platelet reactivity and much higher ratio of clopidogrel real non-response. Switch of therapy may effectively overcome clopidogrel non-response. A new appearance of high platelet reactivity with unknown clinical significance is observed in both groups among the patients on clopidogrel. © 2013 Elsevier Ltd. All rights reserved. Introduction The success of percutaneous coronary intervention therapy requires induction of dual antiplatelet treatment. In the last decade the COX-1 inhibitor aspirin and the P2Y 12 ADP-receptor blocker clopidogrel became the primary choice of treatment to prevent recurrent ischemic events after intracoronary stenting [1–3]. However high variability of individual clopidogrel response raised doubts in „one-size-fits-all” dosing method, therefore clinical benefit of platelet function testing and tailored antiplatelet therapy became an excessively researched field in the past few years. Evidences accumulated that high on-clopidogrel treatment platelet reactivity after intracoronary stenting is an independent risk factor of recurrent ischemic events such as cardiovascular death, myocardial infarction or stent thrombosis [4–11]. Therefore clinical need emerged for measuring the efficacy of antiplatelet therapy and for developing more effective ADP-receptor blocking agents. Thrombosis Research 133 (2014) 257–264 Abbreviations: AA, arachidonic-acid; ACEI, angiotensin-converting-enzyme inhibitor; ACS, acute coronary syndrome; ADP, adenosine-diphosphate; ARB, angiotensin-II receptor blocker; BMI, body mass index; CABG, coronary artery bypass graft; CAD, coronary artery disease; COLL, collagen; COX-1, cyclooxygenase-1; CV, coefficient of variation; DES, drug eluting stent; EPI, epinephrine; HPR, high on-clopidogrel treatment platelet reactivity; LM, left main coronary artery branch; LTA, light transmission aggregometry; MACE, major adverse coronary events; MI, myocardial infarction; NPR, normal platelet reactivity; NSTEMI, non ST segment elevation myocardial infarction; OR, odds ratio; PCI, percutane- ous coronary intervention; PsNR, clopidogrel pseudo non-responder; RNR, clopidogrel real non-responder; rpm, rate per minute; SA, stable angina; STEMI, ST segment elevation myocardial infarction; TIMI, thrombolysis in myocardial infarction; UAP, unstable angina pectoris. ⁎ Corresponding author at: Medical Center, Hungarian Defence Forces, Department of Cardiology, Róbert Károly krt. 44., Budapest, Hungary, H-1134. Tel.: +36 702464686; fax: +36 14651857. E-mail address: leesaci@gmail.com (S. Leé). 0049-3848/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.thromres.2013.11.029 Contents lists available at ScienceDirect Thrombosis Research journal homepage: www.elsevier.com/locate/thromres