University of Florida College of Medicine, Jacksonville, Florida 32209, USA.
J Am Coll Cardiol. 2010 Sep 21;56(13):1017-23. doi: 10.1016/j.jacc.2010.02.072.
The objective was to evaluate the pharmacodynamic response of switching patients on maintenance phase clopidogrel therapy after an acute coronary syndrome (ACS) to prasugrel.
Prasugrel P2Y(12) receptor blockade is associated with greater pharmacodynamic platelet inhibition and reduction of ischemic complications compared with that of clopidogrel in ACS patients undergoing percutaneous coronary intervention. The pharmacodynamic effects of switching patients during maintenance phase clopidogrel therapy after an ACS event to prasugrel are unknown.
The SWAP (SWitching Anti Platelet) study was a phase 2, multicenter, randomized, double-blind, double-dummy, active-control trial. After a run-in of daily open-label clopidogrel 75 mg with aspirin therapy for 10 to 14 days, patients were randomly assigned to 1 of the following 3 treatments: placebo loading dose (LD)/clopidogrel 75 mg maintenance dose (MD), placebo LD/prasugrel 10 mg MD, or prasugrel 60 mg LD/10 mg MD. Platelet function was evaluated at 2 h, 24 h, 7 days, and 14 days using light transmittance aggregometry, VerifyNow P2Y(12) assay, and vasodilator-stimulated phosphoprotein phosphorylation.
A total of 139 patients were randomized, of whom 100 were eligible for analysis. Maximum adenosine diphosphate-induced platelet aggregation (20 μM) by light transmittance aggregometry at 1 week (primary end point) was lower after prasugrel MD compared with clopidogrel MD (41.1% vs. 55.0%, p < 0.0001), and was also lower in the prasugrel LD+MD group compared with clopidogrel MD (41.0% vs. 55.0%, p < 0.0001). At 2 h, a prasugrel LD resulted in higher platelet inhibition compared with the other regimens. Similar results were found using light transmittance aggregometry with 5 μM adenosine diphosphate, VerifyNow P2Y(12), and vasodilator-stimulated phosphoprotein phosphorylation assays.
For patients receiving maintenance clopidogrel therapy after an ACS event, switching from clopidogrel to prasugrel is associated with a further reduction in platelet function by 1 week using prasugrel MD or within 2 h with the administration of a prasugrel LD. (A Pharmacodynamic Comparison of Prasugrel [LY640315] Versus Clopidogrel in Subjects With Acute Coronary Syndrome Who Are Receiving Clopidogrel [SWAP]; NCT00356135).
评估急性冠脉综合征（ACS）后接受维持期氯吡格雷治疗的患者换用普拉格雷的药效学反应。
与氯吡格雷相比，普拉格雷可更大程度地抑制血小板 P2Y(12)受体，减少 ACS 经皮冠状动脉介入治疗患者的缺血性并发症。ACS 事件后换用维持期氯吡格雷治疗的患者，换用普拉格雷的药效学影响尚不清楚。
SWAP（Switching Anti Platelet）研究是一项 2 期、多中心、随机、双盲、双模拟、活性对照试验。在每日开放标签氯吡格雷 75mg 联合阿司匹林治疗 10-14 天后，患者随机分配至以下 3 种治疗之一：安慰剂负荷剂量（LD）/氯吡格雷 75mg 维持剂量（MD）、安慰剂 LD/普拉格雷 10mg MD 或普拉格雷 60mg LD/10mg MD。使用光透射聚集法、VerifyNow P2Y(12)检测和血管扩张刺激磷蛋白磷酸化，分别于 2h、24h、7d 和 14d 评估血小板功能。
共 139 例患者随机分组，其中 100 例符合分析条件。1 周时（主要终点）光透射聚集法检测的最大二磷酸腺苷诱导的血小板聚集（20μM），普拉格雷 MD 组低于氯吡格雷 MD 组（41.1% vs. 55.0%，p<0.0001），普拉格雷 LD+MD 组也低于氯吡格雷 MD 组（41.0% vs. 55.0%，p<0.0001）。2h 时，普拉格雷 LD 较其他方案更能抑制血小板。用 5μM 二磷酸腺苷、VerifyNow P2Y(12)和血管扩张刺激磷蛋白磷酸化检测，也得到了相似的结果。
对于 ACS 事件后接受维持期氯吡格雷治疗的患者，与氯吡格雷相比，换用普拉格雷可使血小板功能进一步降低（普拉格雷 MD 组 1 周时，普拉格雷 LD 组 2h 时）。
