Relationship between smoking and responsiveness to clopidogrel in non-cardiogenic ischemic stroke patients.
OBJECTIVE
Clopidogrel is used to prevent the recurrence of non-cardiogenic ischemic stroke, but individual responsiveness to the drug varies. Moreover, it is known that smoking, which is a risk factor for ischemic stroke, affects the drug's pharmacokinetics. The objective of the present study was to investigate a possible relationship between smoking and responsiveness to clopidogrel in non-cardiogenic ischemic stroke patients.


METHODS
The study involved 209 non-cardiogenic ischemic stroke patients who were administered oral clopidogrel at a dosage of 75 mg/day for at least 1 week. Platelet aggregation in response to adenosine diphosphate (20 μM) was measured in each patient using the VerifyNow P2Y12 Assay. Platelet aggregation and the incidence of resistance to clopidogrel were compared between a smokers group (70 patients) and a non-smokers group (139 patients). Clopidogrel resistance was defined as a P2Y12 Reaction Units (PRU) value >230 and/or % inhibition <20%.


RESULTS
The mean PRU was 128.3±85.5 in the smokers group and 167.7±86.6 in the non-smokers group (p=0.002). The incidence of PRU >230 was 12.9% (9 patients) in the smokers group and 25.9% (36 patients) in the non-smokers group (p=0.033). The mean % inhibition was 48.6±30.7% in the smokers group and 36.9±27.6% in the non-smokers group (p=0.009). The incidence of patients with % inhibition <20% was 24.3% (17 patients) in the smokers group and 34.5% (48 patients) in the non-smokers group (p=0.155).


CONCLUSIONS
The incidence of clopidogrel resistance was lower in the non-cardiogenic ischemic stroke patients who were smokers, thus indicating that these patients' responsiveness to this drug may be enhanced.
Department of Neurology and Cerebrovascular Medicine, Saitama Medical University International Medical Center, Japan.
Hajime
H
Maruyama
Takuya
T
Fukuoka
Ichiro
I
Deguchi
Yasuko
Y
Ohe
Yohsuke
Y
Horiuchi
Yuji
Y
Kato
Yoshihide
Y
Sehara
Yuito
Y
Nagamine
Hiroyasu
H
Sano
Takeshi
T
Hayashi
Norio
N
Tanahashi
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D001780:Blood Coagulation Tests; D000077144:Clopidogrel; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests; D012307:Risk Factors; D012907:Smoking / Q000503:physiopathology*; D020521:Stroke / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine