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Pharmacodynamics (PD) of clopidogrel in patients with acute coronary syndromes undergoing percutaneous interventions (PCI)
Author(s) -
Fuchs I.,
Frossard M.,
Laggner A.,
Spiel A.,
Wohlschläger E.,
Jilma B.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.094
Subject(s) - clopidogrel , medicine , pharmacodynamics , conventional pci , p2y12 , percutaneous coronary intervention , loading dose , cardiology , myocardial infarction , prasugrel , acute coronary syndrome , platelet , pharmacology , pharmacokinetics
Background/Aims Little is known about the PD of clopidogrel in patients suffering from acute coronary syndromes (ACS) undergoing PCI. We hypothesized that the high degree of platelet activation in ACS patients may impede the PD effects of clopidogrel early after onset of ACS. Methods ACS patients (n=200), who presented to the University Hospital, were included into a prospective trial. Patients received a loading dose of clopidogrel (300 mg) followed by 75mg/d clopidogrel up to 12 months. Platelet function was assessed by the collagen adenosine diphosphate closure time (CAPD‐CT) with the FDA approved platelet function analyzer (PFA‐100). The single nucleotide polymorphism (SNP) i‐744 of the purinergic receptor P2Y12 was determined by Taqman technology. Results Baseline CAPD‐CT averaged 99s (CI: 90‐110), and a 10% increase in CADP‐CT was observed only after a time‐lag of 7 days (p=0.03). Maximum effectiveness was observed only after period of 3 months on therapy[CADP‐CT: 154s (138–169); p<0.0001]. The diagnosis of myocardial infarction and high plasma levels of von Willebrand Factor levels predicted decreased responsiveness to clopidogrel therapy, whereas the assessed P2Y12R SNP had no impact. Conclusions Our pharmacodynamic data indicate that ACS patients could profit from higher clopidogrel dosages particularly in the early weeks after PCI, and dose finding studies appear recommendable. Clinical Pharmacology & Therapeutics (2005) 77 , P53–P53; doi: 10.1016/j.clpt.2004.12.094