Gladding Patrick, Webster Mark, Zeng Irene, Farrell Helen, Stewart Jim, Ruygrok Peter, Ormiston John, El-Jack Seif, Armstrong Guy, Kay Patrick, Scott Douglas, Gunes Arzu, Dahl Marja-Liisa
Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand.
JACC Cardiovasc Interv. 2008 Dec;1(6):612-9. doi: 10.1016/j.jcin.2008.09.005.
This study evaluated the antiplatelet effect of a higher loading and maintenance dose regimen of clopidogrel and a possible drug interaction with verapamil.
Clopidogrel loading doses above 600 mg have not resulted in more rapid or complete platelet inhibition. Higher maintenance dosages may be more effective than 75 mg/day.
A double-blind, randomized, placebo-controlled trial was undertaken in 60 patients undergoing percutaneous coronary intervention. All patients received clopidogrel 600 mg at the start of the procedure. Using a 2 x 2 design, patients were allocated to clopidogrel 600 mg given 2 h later or matching placebo, and to verapamil 5 mg intra-arterial or placebo. Platelet function was measured using the VerifyNow P2Y12 analyzer (Accumetrics Ltd., San Diego, California) at 2, 4, and 7 h. Patients were further randomized to receive a clopidogrel 75 or 150 mg once daily, with platelet function assessed after 1 week.
Two hours after the second dose of clopidogrel or placebo, platelet inhibition was 42 +/- 27% with clopidogrel, compared with 24 +/- 22% with placebo (p = 0.0006). By 5 h after the second dose, platelet inhibition was 49 +/- 30% with clopidogrel, compared with 29 +/- 22% with placebo (p = 0.01). No drug interaction was seen with verapamil. A clopidogrel maintenance dosage of 150 mg daily for 1 week resulted in greater platelet inhibition than 75 mg daily (50 +/- 28% vs. 29 +/- 19%, p = 0.01).
In an unselected population undergoing percutaneous coronary intervention a clopidogrel 1,200-mg loading dose, given as two 600-mg doses 2 h apart, results in more rapid and complete platelet inhibition than a single 600-mg dose. A maintenance dosage of 150 mg daily produces greater platelet inhibition than 75 mg daily. (The PRINC trial; ACTRN12606000129583).
本研究评估了氯吡格雷更高负荷剂量和维持剂量方案的抗血小板作用以及与维拉帕米可能存在的药物相互作用。
氯吡格雷负荷剂量超过600 mg并未导致更快或更完全的血小板抑制。更高的维持剂量可能比每日75 mg更有效。
对60例接受经皮冠状动脉介入治疗的患者进行了一项双盲、随机、安慰剂对照试验。所有患者在手术开始时均接受600 mg氯吡格雷。采用2×2设计，患者被分配至在2小时后给予600 mg氯吡格雷或匹配的安慰剂，以及动脉内给予5 mg维拉帕米或安慰剂。在2、4和7小时使用VerifyNow P2Y12分析仪（Accumetrics Ltd.，加利福尼亚州圣地亚哥）测量血小板功能。患者进一步随机分组，接受每日一次75或150 mg氯吡格雷，1周后评估血小板功能。
在给予第二剂氯吡格雷或安慰剂2小时后，氯吡格雷组的血小板抑制率为42±27%，而安慰剂组为24±22%（p = 0.0006）。在给予第二剂5小时后，氯吡格雷组的血小板抑制率为49±30%，而安慰剂组为29±22%（p = 0.01）。未观察到与维拉帕米的药物相互作用。氯吡格雷维持剂量每日150 mg持续1周导致的血小板抑制作用大于每日75 mg（50±28%对29±19%，p = 0.01）。
在未经过筛选的接受经皮冠状动脉介入治疗的人群中，氯吡格雷1200 mg负荷剂量以两个600 mg剂量间隔2小时给药，比单次600 mg剂量导致更快、更完全的血小板抑制。每日150 mg的维持剂量比每日75 mg产生更大程度的血小板抑制。（PRINC试验；ACTRN12606000129583）
