Department of Cardiology, Seoul National University Hospital, Seoul, South Korea.
Am J Cardiovasc Drugs. 2013 Dec;13(6):413-24. doi: 10.1007/s40256-013-0039-y.
Clopidogrel napadisilate has better clopidogrel stability than clopidogrel bisulfate. There are no data, however, on the antiplatelet efficacy and tolerability of clopidogrel napadisilate in coronary artery disease (CAD) patients.
The aim of this study is to demonstrate that the combination therapy of aspirin and clopidogrel napadisilate is not inferior to that of aspirin and clopidogrel bisulfate with respect to its effectiveness in inhibiting platelet aggregation, if it is given for 4 weeks to CAD patients who had been treated with a drug-eluting stent more than 12 months prior and had remained in a stable condition with a single antiplatelet agent, aspirin.
This study was a prospective, randomized, double-blind, double-dummy, parallel-group, phase IV clinical trial. A total of 162 patients were prospectively recruited from three centers. The subjects were randomized to either the test group that was treated with 75 mg of clopidogrel napadisilate once daily or to the control group that was treated with 75 mg of clopidogrel bisulfate once daily. The primary outcome was the percent inhibition of the platelet aggregation change after the medication, as assessed by a VerifyNow™ P2Y12 assay. The secondary outcome was the change in P2Y12 reaction units (PRUs) from the baseline to the end of 4 weeks of treatment. The prevalence of adverse events was assessed at each visit through a direct interview.
The mean increase in the percent inhibition after 4 weeks of treatment was 19.4 % in the clopidogrel napadisilate group and 19.5 % in the clopidogrel bisulfate group. The lower bound of the 95 % two-sided confidence interval for the difference in the change between the two groups (-5.46) was greater than the pre-defined non-inferiority margin of (-10.5). Therefore, clopidogrel napadisilate was deemed non-inferior to clopidogrel bisulfate with respect to its effectiveness in inhibiting platelet aggregation. The PRU decreased by 73.1 ± 30.7 in the clopidogrel napadisilate group, which decreased by -7.8 more than in the clopidogrel bisulfate group (65.3 ± 62.1); but the difference between the two groups was statistically insignificant (p = 0.435). There was no significant difference in the drug-related adverse events between the two groups (12.3 vs. 10.1 %; p = 0.804).
The platelet inhibitory efficacy of clopidogrel napadisilate is not inferior to that of clopidogrel bisulfate. There were also no statistically significant differences between the two treatment groups in the safety analyses. Therefore, clopidogrel napadisilate can be a suitable alternative to clopidogrel bisulfate in stable CAD patients who have undergone a drug-eluting stent placement.
Registered at ClinicalTrials.gov as NCT01830491.
氯吡格雷萘达唑较氯吡格雷二氢硫酸盐更稳定。然而，目前尚无氯吡格雷萘达唑在冠状动脉疾病（CAD）患者中的抗血小板疗效和耐受性数据。
本研究旨在证明，对于在 12 个月前接受药物洗脱支架治疗且仅使用单一抗血小板药物阿司匹林治疗稳定的 CAD 患者，给予氯吡格雷萘达唑联合阿司匹林治疗 4 周，其在抑制血小板聚集方面的疗效不劣于阿司匹林联合氯吡格雷二氢硫酸盐。
这是一项前瞻性、随机、双盲、双模拟、平行组、四期临床试验。从三个中心前瞻性招募了 162 名患者。将受试者随机分为试验组，每天服用 75mg 氯吡格雷萘达唑；或对照组，每天服用 75mg 氯吡格雷二氢硫酸盐。主要结局是通过 VerifyNow™ P2Y12 测定评估的用药后血小板聚集抑制率变化。次要结局是治疗 4 周结束时 P2Y12 反应单位（PRUs）的变化。通过直接访谈在每次就诊时评估不良事件的发生率。
治疗 4 周后，氯吡格雷萘达唑组的血小板抑制率平均增加 19.4%，氯吡格雷二氢硫酸盐组增加 19.5%。两组间差异的 95%双侧置信区间下限（-5.46）大于预设的非劣效性界值（-10.5）。因此，氯吡格雷萘达唑在抑制血小板聚集方面的疗效不劣于氯吡格雷二氢硫酸盐。氯吡格雷萘达唑组的 PRU 下降了 73.1±30.7，比氯吡格雷二氢硫酸盐组下降了-7.8（65.3±62.1）；但两组间差异无统计学意义（p=0.435）。两组间药物相关不良事件无显著差异（12.3%比 10.1%；p=0.804）。
氯吡格雷萘达唑的血小板抑制作用不劣于氯吡格雷二氢硫酸盐。两组在安全性分析中也无统计学差异。因此，氯吡格雷萘达唑可作为稳定 CAD 患者药物洗脱支架置入后氯吡格雷二氢硫酸盐的替代药物。
ClinicalTrials.gov 注册为 NCT01830491。
