High on clopidogrel treatment platelet reactivity is frequent in acute and rare in elective stenting and can be functionally overcome by switch of therapy

Abstract

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 reactivity 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 >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 platelet 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 therapy. 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 benefit 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.

Keywords: AA; ACEI; ACS; ADP; ARB; BMI; CABG; CAD; COLL; COX-1; CV; Clopidogrel; DES; EPI; HPR; LM; LTA; Light transmission aggregometry; MACE; MI; Myocardial infarction; NPR; NSTEMI; OR; PCI; Percutaneous coronary intervention; Platelet reactivity; PsNR; RNR; SA; ST segment elevation myocardial infarction; STEMI; TIMI; Therapy adjustment; UAP; acute coronary syndrome; adenosine-diphosphate; angiotensin-II receptor blocker; angiotensin-converting-enzyme inhibitor; arachidonic-acid; body mass index; clopidogrel pseudo non-responder; clopidogrel real non-responder; coefficient of variation; collagen; coronary artery bypass graft; coronary artery disease; cyclooxygenase-1; drug eluting stent; epinephrine; high on-clopidogrel treatment platelet reactivity; left main coronary artery branch; light transmission aggregometry; major adverse coronary events; myocardial infarction; non ST segment elevation myocardial infarction; normal platelet reactivity; odds ratio; percutaneous coronary intervention; rate per minute; rpm; stable angina; thrombolysis in myocardial infarction; unstable angina pectoris.