Division of Cardiology, University of Florida College of Medicine-Jacksonville.
Circulation. 2019 Apr 2;139(14):1661-1670. doi: 10.1161/CIRCULATIONAHA.118.038317.
The platelet inhibitory effects induced by oral P2Y receptor antagonists are delayed in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention (P-PCI). In turn, this leads to a gap in platelet inhibition, exposing patients to an increased risk of early thrombotic complications and underscoring the need to define strategies associated with more effective platelet inhibition in the peri-primary percutaneous coronary intervention period. Cangrelor is an intravenous P2Y inhibitor with prompt and potent antiplatelet effects. However, to date, there are limited data on the effects of cangrelor used in combination with ticagrelor in patients undergoing primary percutaneous coronary intervention. Moreover, questions have emerged on the potential for drug-drug interactions during the transition from cangrelor to oral P2Y inhibitors.
This was a prospective, randomized, double-blind, placebo-controlled pharmacodynamic study conducted in patients undergoing primary percutaneous coronary intervention (n=50) who were randomized to treatment with either cangrelor or matching placebo (bolus followed by 2-hour infusion). All patients received ticagrelor 180-mg loading dose administered as crushed tablets at the time of cangrelor/placebo bolus administration. Pharmacodynamic analyses were performed at 8 time points. Pharmacodynamic effects were measured as P2Y reaction units by VerifyNow and platelet reactivity index by vasodilator-stimulated phosphoprotein.
Compared with placebo, cangrelor was associated with reduced P2Y reaction units as early as 5 minutes after bolus, which persisted during the entire duration of drug infusion, including at 30 minutes (63 [32-93] versus 214 [183-245]; mean difference, 152 [95% CI, 108-195]; P<0·001; primary end point). Parallel findings were shown with platelet reactivity index. Accordingly, high on-treatment platelet reactivity rates were reduced with cangrelor. After discontinuation of cangrelor/placebo infusion, there were no differences in levels of platelet reactivity between groups, ruling out a drug-drug interaction when cangrelor and ticagrelor are concomitantly administered.
In patients undergoing primary percutaneous coronary intervention, cangrelor is an effective strategy to bridge the gap in platelet inhibition associated with the use of oral P2Y inhibition induced by ticagrelor. Ticagrelor can be administered as a crushed formulation concomitantly with cangrelor without any apparent drug-drug interaction. The clinical implications of these pharmacodynamic findings warrant investigation in an adequately powered clinical trial.
URL: https://www.clinicaltrials.gov . Unique identifier: NCT03247738.
在接受直接经皮冠状动脉介入治疗（P-PCI）的 ST 段抬高型心肌梗死患者中，口服 P2Y 受体拮抗剂诱导的血小板抑制作用延迟。反过来，这导致血小板抑制出现空白，使患者面临早期血栓并发症的风险增加，并强调需要确定与围 P-PCI 期间更有效的血小板抑制相关的策略。坎格雷洛是一种静脉内 P2Y 抑制剂，具有快速和强大的抗血小板作用。然而，迄今为止，关于在接受直接经皮冠状动脉介入治疗的患者中使用坎格雷洛联合替格瑞洛的效果的数据有限。此外，在从坎格雷洛转换为口服 P2Y 抑制剂期间，药物相互作用的可能性引起了关注。
这是一项前瞻性、随机、双盲、安慰剂对照的药效学研究，纳入了 50 名接受直接经皮冠状动脉介入治疗的患者（n=50），这些患者被随机分为坎格雷洛或匹配安慰剂（推注后 2 小时输注）治疗组。所有患者在给予坎格雷洛/安慰剂推注时均接受 180mg 替格瑞洛负荷剂量的压碎片剂给药。在 8 个时间点进行药效学分析。通过 VerifyNow 测定 P2Y 反应单位，通过血管扩张刺激磷蛋白测定血小板反应指数来测量药效学效应。
与安慰剂相比，坎格雷洛在推注后 5 分钟即可降低 P2Y 反应单位，这种作用持续整个药物输注期间，包括在 30 分钟时（63[32-93]与 214[183-245]；平均差异，152[95%CI，108-195]；P<0·001；主要终点）。血小板反应指数也显示出类似的结果。因此，坎格雷洛降低了高治疗时血小板反应率。停用坎格雷洛/安慰剂输注后，两组间血小板反应水平无差异，排除了当坎格雷洛和替格瑞洛同时给药时的药物相互作用。
在接受直接经皮冠状动脉介入治疗的患者中，坎格雷洛是一种有效的策略，可以弥合因替格瑞洛引起的口服 P2Y 抑制而导致的血小板抑制空白。替格瑞洛可以作为压碎制剂与坎格雷洛同时给药，没有明显的药物相互作用。这些药效学发现的临床意义需要在一项充分有力的临床试验中进行研究。
网址：https://www.clinicaltrials.gov 。唯一标识符：NCT03247738。
