Division of Cardiology, Department of Internal Medicine/Cardiovascular Center, Seoul National University Hospital, Seoul, Korea.
Clin Ther. 2013 Jan;35(1):28-37.e4. doi: 10.1016/j.clinthera.2012.12.004.
Clopidogrel bisulfate, a potent antiplatelet agent, has a pivotal role in the prevention and treatment of atherothrombotic disease. Clopidogrel napadisilate, a different salt preparation of clopidogrel, has been developed and approved in Korea and several European countries. Recent studies have suggested that clopidogrel napadisilate might have improved stability and comparable bioequivalence to clopidogrel bisulfate. However, these 2 clopidogrel preparations have not been compared in terms of efficacy and tolerability in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI).
We sought to investigate the antiplatelet efficacy and safety profile of clopidogrel napadisilate compared with clopidogrel bisulfate in CAD patients after PCI.
This was a randomized, multicenter, open-label, Phase IV, noninferiority clinical trial. We prospectively recruited CAD patient in 6 institutions in Korea between October 2010 and November 2011. Patients who underwent PCI were randomly assigned to the test group (clopidogrel napadisilate plus aspirin) or control group (clopidogrel bisulfate plus aspirin). Antiplatelet efficacy and safety profile were assessed after 4 weeks of maintenance treatment. The primary end point was noninferiority of the percentage of P2Y(12) inhibition, measured by point-of-care assay. The rate of major adverse cardiovascular events (MACE), as a secondary end point, was compared between the 2 clopidogrel preparations. To assess tolerability, we evaluated the incidence, severity, and causal relation of adverse events (AEs) of 2 groups.
A total of 169 patients were screened, and 127 patients completed the study (64 in the test group and 63 in the control group; P = 0.296). The baseline characteristics of patients did not differ significantly between the treatment groups. The between-group difference in percentage of P2Y(12) inhibition did not exceed the prespecified limit for noninferiority (P for noninferiority = 0.032; 95% CI, -8.33 to 5.53). With respect to the risk of MACE, no significant difference was found in the incidence of myocardial infarction or stroke between the groups (1 in the test group and 2 in the control group; P > 0.99); no mortality was reported in either group. The tolerability of clopidogrel napadisilate was comparable with that of clopidogrel bisulfate in terms of all AEs, drug-related AEs, and serious AEs (all AEs: test group, 33.3%; control group, 32.9% [P > 0.99]; drug-related AEs: test group, 4.17%; control group, 0% [P = 0.113]; serious AEs: test group, 1.39%; control group, 5.26% [P=0.367]).
In this study of CAD Korean patients who have undergone PCI, the antiplatelet efficacy of clopidogrel napadisilate was noninferior to that of clopidogrel bisulfate after 4 weeks of maintenance treatment. No statistically significant difference was found in tolerability between the 2 treatment groups.
硫酸氢氯吡格雷是一种强效抗血小板药物，在动脉血栓栓塞性疾病的预防和治疗中具有重要作用。氯吡格雷萘二磺酸盐是氯吡格雷的另一种盐制剂，已在韩国和几个欧洲国家开发和批准。最近的研究表明，氯吡格雷萘二磺酸盐可能具有更稳定的特性和与硫酸氢氯吡格雷相当的生物等效性。然而，在接受经皮冠状动脉介入治疗（PCI）的冠心病（CAD）患者中，尚未比较这两种氯吡格雷制剂在疗效和耐受性方面的差异。
我们旨在研究氯吡格雷萘二磺酸盐与硫酸氢氯吡格雷在接受 PCI 的 CAD 患者中的抗血小板疗效和安全性特征。
这是一项随机、多中心、开放性、IV 期、非劣效性临床试验。我们于 2010 年 10 月至 2011 年 11 月在韩国的 6 家机构前瞻性招募 CAD 患者。接受 PCI 的患者被随机分配到试验组（氯吡格雷萘二磺酸盐加阿司匹林）或对照组（硫酸氢氯吡格雷加阿司匹林）。在维持治疗 4 周后评估抗血小板疗效和安全性特征。主要终点是通过即时检测法评估的 P2Y12 抑制率的非劣效性。次要终点是比较两种氯吡格雷制剂之间的主要不良心血管事件（MACE）发生率。为了评估耐受性，我们评估了两组不良事件（AE）的发生率、严重程度和因果关系。
共筛选了 169 名患者，127 名患者完成了研究（试验组 64 名，对照组 63 名；P=0.296）。患者的基线特征在治疗组之间无显著差异。两组之间 P2Y12 抑制率的差异未超过非劣效性的预设限值（非劣效性 P=0.032；95%CI，-8.33 至 5.53）。关于 MACE 的风险，两组心肌梗死或中风的发生率无显著差异（试验组 1 例，对照组 2 例；P＞0.99）；两组均无死亡报告。氯吡格雷萘二磺酸盐的耐受性与硫酸氢氯吡格雷相当，所有 AE、药物相关 AE 和严重 AE 的发生率均相似（所有 AE：试验组 33.3%，对照组 32.9%[P＞0.99]；药物相关 AE：试验组 4.17%，对照组 0%[P=0.113]；严重 AE：试验组 1.39%，对照组 5.26%[P=0.367]）。
在这项接受 PCI 的韩国 CAD 患者的研究中，氯吡格雷萘二磺酸盐在维持治疗 4 周后的抗血小板疗效不劣于硫酸氢氯吡格雷。两组治疗的耐受性无统计学差异。
