title: Time-related changes in determinants of antiplatelet effect of clopidogrel in patients after myocardial infarction.
abstract: Substantial variability of antiplatelet action is an important limitation of clopidogrel. The aim of this study was to evaluate time-related changes in determinants of clopidogrel responsiveness in patients after myocardial infarction. The study population comprised 191 consecutive patients treated with primary percutaneous coronary intervention for acute myocardial infarction. Follow-up visits were scheduled at 3, 6 and 9 months after discharge. ADP-induced platelet aggregation was tested with Multiplate Analyzer. Patients with ADP-PA>46.8U were defined as clopidogrel non-responders. The prevalence of clopidogrel non-responsiveness was highest during hospitalization and at 9 month follow-up visit, while it was lowest at 3 and 6 months after myocardial infarction (P=0.004). According to multivariate analysis, platelet count, mean platelet volume, concentration of hsCRP and leukocyte count influenced ADP-induced platelet aggregation in multiple assessment points. BMI, concentrations of hemoglobin, glycated hemoglobin, and BNP, hematocrit, adherence to medication, and patient׳s age were found to be independent predictors of high on-treatment ADP-induced platelet aggregation only at a single follow-up visit. Determinants of clopidogrel responsiveness in patients after myocardial infarction change within the long-term therapy. During hospitalization and early after discharge only biological factors affect ADP-induced platelet aggregation, while non-adherence to antiplatelet therapy may be a significant factor in determining clopidogrel non-responsiveness during late follow-up visits.
authors.affiliation: Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, 3 Techników Street, 85-801 Bydgoszcz, Poland. Electronic address: aldona.kubica@gmail.com.
authors.forename: Aldona
authors.initials: A
authors.lastname: Kubica
authors.affiliation: Department of Pharmacology and Therapy, Collegium Medicum, Nicolaus Copernicus University, 9M. Skłodowskiej-Curie Street, 85-094 Bydgoszcz, Poland; Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, 9M. Skłodowskiej-Curie Street, 85-094 Bydgoszcz, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Kasprzak
authors.affiliation: Department of Cardiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Siller-Matula
authors.affiliation: Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, 9M. Skłodowskiej-Curie Street, 85-094 Bydgoszcz, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Koziński
authors.affiliation: Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, 9M. Skłodowskiej-Curie Street, 85-094 Bydgoszcz, Poland.
authors.forename: Eliano
authors.initials: E
authors.lastname: Pio Navarese
authors.affiliation: Department of Pharmacology and Therapy, Collegium Medicum, Nicolaus Copernicus University, 9M. Skłodowskiej-Curie Street, 85-094 Bydgoszcz, Poland; Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, 9M. Skłodowskiej-Curie Street, 85-094 Bydgoszcz, Poland. Electronic address: kalaobonska@op.pl.
authors.forename: Karolina
authors.initials: K
authors.lastname: Obońska
authors.affiliation: Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, 3 Techników Street, 85-801 Bydgoszcz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Andruszkiewicz
authors.affiliation: National Health Fund, 4A/30 Chołoniewskiego Street, 85-127 Bydgoszcz, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Sztuba
authors.affiliation: Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, 9M. Skłodowskiej-Curie Street, 85-094 Bydgoszcz, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Fabiszak
authors.affiliation: Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, 9M. Skłodowskiej-Curie Street, 85-094 Bydgoszcz, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Swiątkiewicz
authors.affiliation: Department of Emergency Medicine, Collegium Medicum, Nicolaus Copernicus University, 9M. Skłodowskiej-Curie Street, 85-094 Bydgoszcz, Poland.
authors.forename: Przemysław
authors.initials: P
authors.lastname: Paciorek
authors.affiliation: Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, 9M. Skłodowskiej-Curie Street, 85-094 Bydgoszcz, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Kubica
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D000077144:Clopidogrel; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy* / Q000628:therapy; D062645:Percutaneous Coronary Intervention; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011446:Prospective Studies; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: ADP-induced platelet aggregation; Clopidogrel; Effectiveness of antiplatelet therapy; Myocardial infarction