Platelet inhibition by adjunctive cilostazol suppresses the frequency of cerebral ischemic lesions after carotid artery stenting in patients with carotid artery stenosis.
OBJECTIVE
Optimal platelet inhibition is an important therapeutic adjunct in patients with carotid artery stenosis undergoing carotid artery stenting (CAS). Clopidogrel resistance is associated with increased periprocedural thromboembolic complications from neurovascular stent placement procedures. The addition of cilostazol to dual antiplatelet therapy (DAT) has been reported to reduce platelet reactivity and to improve clinical outcomes after percutaneous coronary intervention. This study was undertaken to evaluate the impact of adjunctive cilostazol in patients with CAS.


METHODS
Platelet function was assessed by light transmittance aggregometry using the VerifyNow assay. Sixty-four consecutive patients who underwent CAS received standard DAT, clopidogrel (75 mg daily), and aspirin (100 mg daily) more than 4 weeks before the procedure. From 2010 to 2011 (period I), 28 patients underwent CAS under standard DAT. From 2011 to 2013 (period II), 36 patients prospectively had preoperative assessment of platelet function, and 13 patients with clopidogrel resistance received adjunctive cilostazol (200 mg daily) in addition to standard DAT. The incidence of new ipsilateral ischemic lesions on diffusion-weighted imaging a day after CAS and ischemic or hemorrhagic events within 30 days was assessed.


RESULTS
Clopidogrel resistance was indentified in 12 patients (43%) in period I and 13 patients (36%) in period II (P = .615). In period II, the addition of cilostazol significantly decreased P2Y12 reaction units and % inhibition (P = .006 and P = .005, respectively), and there was a significant difference in P2Y12 reaction units between the two periods. New ipsilateral ischemic lesions were significantly decreased in period II (2/36 patients) compared with period I (7/28 patients; P = .034); however, there was no significant difference in hemorrhagic and thromboembolic events between the two periods.


CONCLUSIONS
Adjunctive cilostazol (triple antiplatelet therapy) in clopidogrel-resistant patients reduces the rate of clopidogrel resistance and suppresses new ischemic lesions without hemorrhagic complications, as compared with standard DAT. Antiplatelet management based on the evaluation of antiplatelet resistance would be required for prevention of perioperative thromboembolic complications in CAS.
Department of Neurosurgery, Nara Medical University, Nara, Japan. Electronic address: nakagawa@nmu-gw.naramed-u.ac.jp.
Ichiro
I
Nakagawa
Department of Radiology, Nara Medical University, Nara, Japan.
Takeshi
T
Wada
Department of Neurosurgery, Nara Medical University, Nara, Japan.
Hun Soo
HS
Park
Department of Neurosurgery, Nara Medical University, Nara, Japan.
Fumihiko
F
Nishimura
Department of Neurosurgery, Nara Medical University, Nara, Japan.
Syuichi
S
Yamada
Department of Radiology, Nara Medical University, Nara, Japan.
Hiroyuki
H
Nakagawa
Department of Radiology, Nara Medical University, Nara, Japan.
Kimihiko
K
Kichikawa
Department of Neurosurgery, Nara Medical University, Nara, Japan.
Hiroyuki
H
Nakase
D000368:Aged; D017130:Angioplasty / Q000009:adverse effects / Q000295:instrumentation*; D001241:Aspirin / Q000627:therapeutic use; D002545:Brain Ischemia / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D016893:Carotid Stenosis / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D000077407:Cilostazol; D000077144:Clopidogrel; D038524:Diffusion Magnetic Resonance Imaging; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011446:Prospective Studies; D015607:Stents; D013777:Tetrazoles / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D000077144:Clopidogrel; D000077407:Cilostazol; D013988:Ticlopidine; D001241:Aspirin