Tajima Hayato, Izumi Takashi, Miyachi Shigeru, Matsubara Noriaki, Ito Masashi, Imai Tasuku, Nishihori Masahiro, Shintai Kazunori, Okamoto Sho, Araki Yoshio, Kumakura Yasuo, Furukawa-Hibi Yoko, Yamada Kiyofumi, Wakabayashi Toshihiko
Department of Neurosurgery, Handa City Hospital, Handa, Japan.
Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Nagoya J Med Sci. 2018 May;80(2):207-215. doi: 10.18999/nagjms.80.2.207.
We investigated the association between genotype and additional effect of cilostazol on clopidogrel resistance (CR) in neuroendovascular therapy. Between January 2012 and January 2016, 447 consecutive patients were administered with 75-mg cilostazol/day. The VerifyNow System was used for evaluating P2Y12 reaction units (PRU) > 230 and/or percentage inhibition of platelet function (% Inhibition) ≤ 20 as CR. Among 158 patients with CR, 31 were administered with additional 100- or 200-mg cilostazol/day and their platelet function was evaluated. According to genotypes revealed using the Spartan RX and DNeasy Blood & Tissue Kit, patients were classified into three phenotypic groups: extensive metabolizer (EM, three patients), intermediate metabolizer (IM, 12 patients), and poor metabolizer (PM, 16 patients). Administration of additional cilostazol decreased PRU (EM group: 160.7 ± 85.2 after vs 278.3 ± 40.1 before, = 0.15; IM group: 205.6 ± 74.0 vs 254.3 ± 35.0, = 0.02; and PM group: 227.8 ± 52.2 vs 282.1 ± 30.4, = 0.003), and increased % Inhibition (EM group: 40.0 ± 27.9 vs 9.3 ± 3.8, = 0.25; IM group: 31.4 ± 18.0 vs 11.8 ± 8.2, = 0.001; and PM group: 24.6 ± 15.0 vs 10.4 ± 9.3, = 0.001). However, the rate of normalized-clopidogrel response, thromboembolic lesions, and bleeding complications were not significantly different among the three groups. Thus, the addition of cilostazol was effective on CR in terms of PRU, % Inhibition, rate of change of normalized-clopidogrel response, thromboembolic events, and bleeding complications irrespective of phenotype.
我们研究了西洛他唑基因型与神经血管内治疗中其对氯吡格雷抵抗（CR）的附加作用之间的关联。2012年1月至2016年1月期间，连续447例患者接受每日75毫克西洛他唑治疗。使用VerifyNow系统将P2Y12反应单位（PRU）>230和/或血小板功能抑制百分比（%抑制）≤20评估为CR。在158例CR患者中，31例患者额外接受每日100或200毫克西洛他唑治疗，并评估其血小板功能。根据使用Spartan RX和DNeasy Blood & Tissue试剂盒揭示的基因型，患者被分为三个表型组：广泛代谢者（EM，3例患者）、中间代谢者（IM，12例患者）和慢代谢者（PM，16例患者）。额外给予西洛他唑可降低PRU（EM组：治疗后为160.7±85.2，治疗前为278.3±40.1，P = 0.15；IM组：205.6±74.0对254.3±35.0，P = 0.02；PM组：227.8±52.2对282.1±30.4，P = 0.003），并增加%抑制（EM组：40.0±27.9对9.3±3.8，P = 0.25；IM组：31.4±18.0对11.8±8.2，P = 0.001；PM组：24.6±15.0对10.4±9.3，P = 0.001）。然而，三组之间氯吡格雷反应正常化率、血栓栓塞性病变和出血并发症并无显著差异。因此，无论表型如何，添加西洛他唑在PRU、%抑制、氯吡格雷反应正常化变化率、血栓栓塞事件和出血并发症方面对CR均有效。
