title: [Resistance to antiplatelet agents assessed by a point-of-care platelet function test and thromboembolic adverse events in neurointervention].
abstract: OBJECTIVE
  To clarify the frequency of Japanese patients who are resistant to antiplatelet agents, and then clarify correlations between resistance and thromboembolic adverse events in neurointervention.
  
  
  METHODS
  Blood samples were collected from 163 patients who were taking antiplatelet agents and received neurointervention, with 128 samples collected just before neurointervention. Residual platelet function was measured using a point-of-care platelet function test, VerifyNow®, and then the frequency of patients resistant to drugs (low-responders), correlations between resistance and thromboembolic events, and effects of adding cilostazol to clopidogrel administration were analyzed. Cut-off values were defined as 550 Aspirin Reaction Units (ARU), 230 P2Y12 Reaction Units (PRU), and 50%inhibition of P2Y12, respectively.
  
  
  RESULTS
  Three of 105 patients (2.9%) taking aspirin at 100 mg/day were low-responders, whereas 48 (41.0%, as measured by PRU) or 80 (68.4%, as measured by %inhibition) of 117 patients taking clopidogrel at 75 mg/day were low-responders. Among the 19 patients taking cilostazol 200 mg/day in addition to clopidogrel 75 mg/day, platelet functions were significantly more strongly inhibited compared to patients taking clopidogrel alone (p=0.02 by PRU, p=0.005 by %inhibition). Thromboembolic adverse events occurred in 7 patients. Among these 7 patients, 6 who were taking aspirin were all responders to aspirin, while 4 of the 6 patients taking clopidogrel were low-responders to clopidogrel. In 69 patients who received aneurysmal transarterial embolization, 2 thromboembolic complications occurred among low-responders (p=0.09).
  
  
  CONCLUSIONS
  Aspirin resistance is rare in Japanese individuals. With aneurysmal transarterial embolization, thromboembolic events tended to occur among clopidogrel low-responders. Addition of cilostazol may offer one method of overcoming clopidogrel resistance.
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Haraguchi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyachi
authors.forename: Takashi
authors.initials: T
authors.lastname: Izumi
authors.forename: Noriaki
authors.initials: N
authors.lastname: Matsubara
authors.forename: Takehiro
authors.initials: T
authors.lastname: Naito
authors.forename: Takumi
authors.initials: T
authors.lastname: Asai
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamanouchi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Wakabayashi
mesh_terms: D000328:Adult; D000368:Aged; D001241:Aspirin / Q000494:pharmacology; D000077407:Cilostazol; D000077144:Clopidogrel; D004351:Drug Resistance; D005260:Female; D006801:Humans; D002532:Intracranial Aneurysm / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010979:Platelet Function Tests / Q000379:methods*; D019095:Point-of-Care Systems; D013777:Tetrazoles / Q000627:therapeutic use; D013923:Thromboembolism / Q000209:etiology*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D000077144:Clopidogrel; D000077407:Cilostazol; D013988:Ticlopidine; D001241:Aspirin