Flierl Ulrike, Zauner Florian, Sieweke Jan-Thorben, Berliner Christine, Napp L Christian, Tillmanns Jochen, Bauersachs Johann, Schäfer Andreas
Prof. Dr. Andreas Schäfer, Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Straße 1, 30625 Hannover, Germany, Tel.: +49 511 532 5240, Fax: +49 511 532 8244, E-mail:
Thromb Haemost. 2017 Jan 5;117(1):99-104. doi: 10.1160/TH16-07-0569. Epub 2016 Oct 13.
Prasugrel, a potent thienopyridine, achieves stronger inhibition of platelet activation than clopidogrel. However, onset of inhibition is significantly delayed in patients with acute ST-elevation myocardial infarction (STEMI), as haemodynamic instability and morphine application seem to exhibit significant influence. Since rapid onset of effect was demonstrated in non-STEMI patients when prasugrel was administered only after percutaneous coronary intervention (PCI) without increasing cardiovascular event rates we assessed the efficacy of prasugrel loading immediately after PCI for STEMI instead of pre-loading before revascularisation. We investigated 50 consecutive patients with acute STEMI (mean age 56 ± 10 years) admitted for primary PCI. Prasugrel efficacy was assessed by platelet reactivity index (PRI; VASP assay) before, 1, 2, 4, 6, 12, and 24 hours following an oral loading dose of 60 mg immediately after PCI. High on-treatment platelet reactivity (HTPR) was defined as PRI>50 %. Prasugrel significantly and rapidly reduced platelet reactivity in acute STEMI patients (p<0.0001 at each time point vs control). Morphine application resulted in a significantly higher HTPR rate among patients having received morphine less than 1 hour before prasugrel loading (p<0.001) while concomitant metoclopramide (MCP) treatment did not significantly affect prasugrel efficacy. In conclusion, in contrast to previous reports describing a significant delay in onset of prasugrel-mediated P2Y inhibition in acute STEMI, we observed a rapid onset with low HTPR rates comparable to those observed in stable non-STEMI patients. Prasugrel administered directly after primary PCI might therefore be a useful therapeutic strategy in patients with STEMI to provide strong and effective P2Y inhibition.
普拉格雷是一种强效噻吩并吡啶类药物，对血小板活化的抑制作用比氯吡格雷更强。然而，急性ST段抬高型心肌梗死（STEMI）患者的抑制作用起效明显延迟，因为血流动力学不稳定和使用吗啡似乎有显著影响。由于在非STEMI患者中，仅在经皮冠状动脉介入治疗（PCI）后给予普拉格雷时显示出快速起效且不增加心血管事件发生率，我们评估了在STEMI患者PCI后立即给予负荷剂量普拉格雷而非在血运重建前预负荷的疗效。我们研究了50例因首次PCI入院的急性STEMI连续患者（平均年龄56±10岁）。在PCI后立即口服60mg负荷剂量后，于1、2、4、6、12和24小时，通过血小板反应性指数（PRI；VASP检测法）评估普拉格雷的疗效。高治疗期血小板反应性（HTPR）定义为PRI>50%。普拉格雷显著且迅速降低了急性STEMI患者的血小板反应性（与对照组相比，各时间点p<0.0001）。在普拉格雷负荷剂量前不到1小时接受吗啡治疗的患者中，使用吗啡导致HTPR发生率显著更高（p<0.001），而同时使用甲氧氯普胺（MCP）治疗并未显著影响普拉格雷的疗效。总之，与之前描述普拉格雷介导的P2Y抑制在急性STEMI中起效明显延迟的报道相反，我们观察到其起效迅速，HTPR发生率低，与稳定的非STEMI患者中观察到的情况相当。因此，在首次PCI后直接给予普拉格雷可能是STEMI患者中一种有用的治疗策略，以提供强效且有效的P2Y抑制。
