title: Diurnal variation in platelet inhibition by clopidogrel.
abstract: Morning increase in the occurrence of myocardial infarction, stroke and sudden cardiac death is a well-recognized phenomenon, which is in line with a morning enhancement of platelet aggregation. We investigated whether platelet inhibition during clopidogrel and aspirin therapy varies during the day. Fifty-nine consecutive patients (45 men and 14 women) with first ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary interventions (pPCI) on dual antiplatelet therapy were prospectively enrolled into the study. Blood samples were collected 4 days after start of clopidogrel treatment at 6.00 a.m., 10.00 a.m., 2.00 p.m. and 7.00 p.m. Arachidonic acid and adenosine diphosphate (ADP)-induced platelet aggregation were assessed by impedance aggregometry. Platelet inhibition by clopidogrel was lowest in the midmorning: median ADP-induced platelet aggregation was 55%, 17% and 27% higher at 10.00 a.m. compared to 6.00 a.m., 2.00 p.m. and 7.00 p.m., respectively (p < 0.002). Nonresponsiveness to clopidogrel defined according to the device manufacturer was 2.4-fold more frequent in the midmorning than in the early morning. We observed a more pronounced midmorning increase in ADP-induced platelet aggregation in diabetic patients when compared to non-diabetics. In contrast, no diurnal variation in the antiplatelet effect of aspirin was observed. In conclusion, in patients presenting with STEMI undergoing pPCI, platelet inhibition by clopidogrel is less strong in the midmorning hours. This periodicity in platelet aggregation in patients on dual antiplatelet therapy should be taken into consideration when assessing platelet function in clinical studies.
authors.affiliation: Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Poland. marekkozinski@wp.pl
authors.forename: Marek
authors.initials: M
authors.lastname: Kozinski
authors.forename: Liliana
authors.initials: L
authors.lastname: Bielis
authors.forename: Joanna
authors.initials: J
authors.lastname: Wisniewska-Szmyt
authors.forename: Joanna
authors.initials: J
authors.lastname: Boinska
authors.forename: Wioleta
authors.initials: W
authors.lastname: Stolarek
authors.forename: Agata
authors.initials: A
authors.lastname: Marciniak
authors.forename: Aldona
authors.initials: A
authors.lastname: Kubica
authors.forename: Zofia
authors.initials: Z
authors.lastname: Grabczewska
authors.forename: Eliano Pio
authors.initials: EP
authors.lastname: Navarese
authors.forename: Felicita
authors.initials: F
authors.lastname: Andreotti
authors.forename: Jolanta Maria
authors.initials: JM
authors.lastname: Siller-Matula
authors.forename: Danuta
authors.initials: D
authors.lastname: Rosc
authors.forename: Jacek
authors.initials: J
authors.lastname: Kubica
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects*; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine