Influence of Diabetes Mellitus and Cigarette Smoking on Variability of the Clopidogrel-Induced Antiplatelet Effect and Efficacy of Active Management of the Target P2Y12 Reaction Unit Range in Patients Undergoing Neurointerventional Procedures.
BACKGROUND
Optimal antiplatelet inhibition is essential in patients undergoing neurointerventional procedures; however, variability in response to clopidogrel can contribute to thromboembolic and hemorrhagic complications. The present study evaluated the influence of diabetes mellitus and cigarette smoking on clopidogrel reactivity.


METHODS
Between 2011 and 2013, 71 consecutive patients underwent aneurysmal coil embolization (CE) or carotid artery stenting (CAS) and received clopidogrel (75 mg daily) and aspirin (100 mg daily) before the treatment. The patients were divided into 2 groups: CE (n = 31) and CAS (n = 40). The patients underwent prospective assessment of preoperative platelet function using VerifyNow assay and received adjunctive cilostazol (200 mg daily, triple antiplatelet therapy) in case of clopidogrel hyporesponse. Patients with clopidogrel hyper-response underwent clopidogrel dose reduction (clopidogrel, 12.5-50 mg daily).


RESULTS
Clopidogrel resistance was noted in 15 patients (37.5%) in the CAS group and in 4 patients (12.9%) in the CE group (P = .031). Clopidogrel hyper-response was noted in 2 patients (5%) in the CAS group and in 11 patients (54.8%) in the CE group (P < .001). There was a significant difference in the baseline clinical characteristics between the 2 groups. In the multivariate logistic regression analysis, diabetes and age were independent predictors of clopidogrel hyporesponse, whereas current smoker was an independent predictor of clopidogrel hyper-response.


CONCLUSIONS
Significant differences in baseline clinical characteristics were present when comparing patients undergoing endovascular treatment of unruptured cerebral aneurysms and carotid artery stenosis. Diabetes mellitus and current smoker status were independent factors related to reactivity to clopidogrel.
Department of Neurosurgery, Nara Medical University, Nara, Japan. Electronic address: nakagawa@nmu-gw.naramed-u.ac.jp.
Ichiro
I
Nakagawa
Department of Neurosurgery, Nara Medical University, Nara, Japan.
Hun Soo
HS
Park
Department of Neurosurgery, Nara Medical University, Nara, Japan.
Shohei
S
Yokoyama
Department of Radiology, Nara Medical University, Nara, Japan.
Takeshi
T
Wada
Department of Neurosurgery, Nara Medical University, Nara, Japan.
Yasuo
Y
Hironaka
Department of Neurosurgery, Nara Medical University, Nara, Japan.
Yasushi
Y
Motoyama
Department of Radiology, Nara Medical University, Nara, Japan.
Katsutoshi
K
Takayama
Department of Radiology, Nara Medical University, Nara, Japan.
Kimihiko
K
Kichikawa
Department of Neurosurgery, Nara Medical University, Nara, Japan.
Hiroyuki
H
Nakase
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use; D016893:Carotid Stenosis / Q000097:blood / Q000601:surgery; D000077407:Cilostazol; D000077144:Clopidogrel; D003920:Diabetes Mellitus / Q000097:blood*; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004621:Embolization, Therapeutic; D005260:Female; D006801:Humans; D002532:Intracranial Aneurysm / Q000097:blood / Q000628:therapy; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011292:Premedication; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012907:Smoking / Q000097:blood*; D015607:Stents; D013777:Tetrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D013777:Tetrazoles; D000077144:Clopidogrel; D000077407:Cilostazol; D013988:Ticlopidine; D001241:Aspirin
Neurointervention; environmental factor; platelet reactivity; target P2Y12 reaction unit