Aleil Boris, Jacquemin Laurent, De Poli Fabien, Zaehringer Michel, Collet Jean-Philippe, Montalescot Gilles, Cazenave Jean-Pierre, Dickele Marie-Claude, Monassier Jean-Pierre, Gachet Christian
Institut National de la Santé et de la Recherche Médicale U311, Etablissement Français du Sang-Alsace, Strasbourg, France.
JACC Cardiovasc Interv. 2008 Dec;1(6):631-8. doi: 10.1016/j.jcin.2008.09.004.
We investigated whether maintenance therapy with clopidogrel 150 mg/day produces greater platelet inhibition than the standard 75-mg/day dose and whether the higher maintenance dose increases platelet inhibition in low responders to clopidogrel 75 mg/day.
Patients show interindividual variability in their platelet response to clopidogrel. Low responders could potentially obtain greater clinical benefit from greater doses of clopidogrel.
One hundred fifty-three elective percutaneous coronary intervention patients were randomized to clopidogrel 150 mg/day (n = 58) or 75 mg/day (n = 95) for 4 weeks, with vasodilator-stimulated phosphoprotein assay-guided switching to clopidogrel 150 mg/day after 2 weeks in low responders (platelet reactivity index >or=69%). All patients received aspirin 75 mg/day.
After 2 weeks, clopidogrel 150 mg/day produced a significantly lower platelet reactivity index than clopidogrel 75 mg/day (43.9 +/- 17.3% vs. 58.6 +/- 17.7%; p < 0.0001). The proportion of low responders was significantly lower in patients randomized to clopidogrel 150 mg/day than in those randomized to clopidogrel 75 mg/day (8.6% vs. 33.7%; p = 0.0004). In the clopidogrel 75 mg/day group, 64.5% (20 of 31) of low responders became responders after switching to clopidogrel 150 mg/day for 2 weeks. No major bleeds occurred during the study; the incidence of minor bleeds was similar in each treatment group.
In elective percutaneous coronary intervention patients, a 150-mg/day clopidogrel maintenance dose produces greater inhibition of platelet function than clopidogrel 75 mg/day. In low responders to clopidogrel 75 mg/day, switching to clopidogrel 150 mg/day overcomes low responsiveness in a majority of patients. These findings warrant further clinical evaluation. (VASP-02; EudraCT number: 2004-005230-40).
我们研究了每日150毫克氯吡格雷维持治疗是否比标准的每日75毫克剂量产生更强的血小板抑制作用，以及更高的维持剂量是否能增强对每日75毫克氯吡格雷反应低下者的血小板抑制作用。
患者对氯吡格雷的血小板反应存在个体差异。反应低下者可能从更大剂量的氯吡格雷中获得更大的临床益处。
153例择期经皮冠状动脉介入治疗患者被随机分为每日150毫克氯吡格雷组（n = 58）或每日75毫克氯吡格雷组（n = 95），治疗4周，对于反应低下者（血小板反应指数≥69%），在2周后根据血管扩张剂刺激磷蛋白分析结果指导转换为每日150毫克氯吡格雷治疗。所有患者均接受每日75毫克阿司匹林治疗。
2周后，每日150毫克氯吡格雷组的血小板反应指数显著低于每日75毫克氯吡格雷组（43.9±17.3%对58.6±17.7%；p < 0.0001）。随机接受每日150毫克氯吡格雷治疗的患者中反应低下者的比例显著低于随机接受每日75毫克氯吡格雷治疗的患者（8.6%对33.7%；p = 0.0004）。在每日75毫克氯吡格雷组中，64.5%（31例中的20例）反应低下者在转换为每日150毫克氯吡格雷治疗2周后变为反应正常者。研究期间未发生严重出血事件；各治疗组轻微出血的发生率相似。
在择期经皮冠状动脉介入治疗患者中，每日150毫克氯吡格雷维持剂量比每日75毫克氯吡格雷产生更强的血小板功能抑制作用。对于每日75毫克氯吡格雷反应低下者，转换为每日150毫克氯吡格雷可使大多数患者克服反应低下的情况。这些发现值得进一步的临床评估。（VASP - 02；欧盟临床试验编号：2004 - 005230 - 40）
