engleski

Repeated clopidogrel loading doses and high maintenance dose after stenting in acute coronary syndrome patients with persistent low response to clopidogrel – a six month follow-up safety study

Introduction: Platelet response to clopidogrel has wide interindividual variability. Low response to clopidogrel is recognized as a significant risk factor for new ischemic events. We sought to investigate whether repeated clopidogrel loading regimen and high maintenance dose (300 mg/day) is safe in persistent low responders on clopidogrel after successful PCI in acute coronary syndrome (ACS) during the period of 6 months. Materials and methods: Patients with ACS who underwent successful coronary stenting were tested with impedance aggregometer - MultiplateR analyzer 12-24 hours after PCI. Exclusion criteria were predefined as follows: thrombocytopenia (<150x10E9/L), significant renal insufficiency (creatinine>200 mcmol/L), advanced age (>80 years), history of intracranial bleeding, history of ischemic cerebrovascular insult (CVI) 6 months prior, concomitant chronic anitcoagulation therapy and continuous postinterventional glycoprotein IIbIIIa receptor antagonist infusion. Cut-off value for clopidogrel low response was 46U as set by consensus statement. Identified low responders received another loading dose of clopidogrel and underwent platelet function testing (PFT) again the following day. Remaining low responders received the third loading dose followed by a maintenance dose of 150 mg/day. On day 7, we repeated PFT and patients who remained low responders on clopidogrel were assigned to maintenance dose of 300 mg/day. Patients older than 70 remained on 150 mg/day. One, two, three and six months after PCI we conducted control PFT and interview to asses platelet reactivity, compliance to treatment and bleeding events according to BARC classification. Results: We enrolled 43 low responders to clopidogrel. Persistent low response was present in 8 patients after one week (18.6%). After 1, 2, 3 and 6 months low response on clopidogrel was found in 5, 3, 2 and 1 patient, respectively. No patient had a major bleeding event. One patient died before first month visit (ischemic CVI). Conclusion: Our study indicates that repeated clopidogrel loading doses and very high maintenance dose could be safe in persistent low responders on clopidogrel in terms of occurrence of major bleeding complications. Maintaining high doses of clopidogrel in late post PCI period might prevail high on-treatment platelet reactivity phenotype in certain patients but some patients are still inadequately treated. Using new P2Y12 inhibitors like ticagrelor and prasugrel should be used in such patients if available.

clopidogrel; acute coronary syndrome; platelet function testing; personalized treatment; safety

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