Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
Department of Cardiology, Amsterdam University Medical Center, Amsterdam, the Netherlands.
JACC Cardiovasc Interv. 2021 Jun 28;14(12):1323-1333. doi: 10.1016/j.jcin.2021.04.022.
This study sought to compare the pharmacodynamic effects of pre-hospitally administered P2Y inhibitor prasugrel in crushed versus integral tablet formulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI).
Early dual antiplatelet therapy is recommended in STEMI patients. Yet, onset of oral P2Y inhibitor effect is delayed and varies according to formulation administered.
The COMPARE CRUSH (Comparison of Pre-hospital Crushed Versus Uncrushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Interventions) trial randomized patients with suspected STEMI to crushed or integral prasugrel 60-mg loading dose in the ambulance. Pharmacodynamic measurements were performed at 4 time points: before antiplatelet treatment, at the beginning and end of pPCI, and 4 h after study treatment onset. The primary endpoint was high platelet reactivity at the end of pPCI. The secondary endpoint was impact of platelet reactivity status on markers of coronary reperfusion.
A total of 441 patients were included. In patients with crushed prasugrel, the occurrence of high platelet reactivity at the end of pPCI was reduced by almost one-half (crushed 34.7% vs. uncrushed 61.6%; odds ratio [OR] = 0.33; 95% confidence interval [CI] = 0.22 to 0.50; p < 0.01). Platelet reactivity <150 P2Y reactivity units at the beginning of coronary angiography correlated with improved Thrombolysis In Myocardial Infarction flow grade 3 in the infarct artery pre-pPCI (OR: 1.78; 95% CI: 1.08 to 2.94; p = 0.02) but not ST-segment resolution (OR: 0.80; 95% CI: 0.48 to 1.34; p = 0.40).
Oral administration of crushed compared with integral prasugrel significantly improves platelet inhibition during the acute phase in STEMI patients undergoing pPCI. However, a considerable number of patients still exhibit inadequate platelet inhibition at the end of pPCI, suggesting the need for alternative agents to bridge the gap in platelet inhibition.
本研究旨在比较院前给予 ST 段抬高型心肌梗死（STEMI）患者经皮冠状动脉介入治疗（pPCI）前施用的 P2Y 抑制剂普拉格雷压碎片与整片制剂的药效学效果。
STEMI 患者推荐早期双联抗血小板治疗。然而，口服 P2Y 抑制剂的作用起效时间延迟，并根据所施用的制剂而变化。
COMPARE CRUSH（STEMI 患者行 pPCI 前接受压碎与未压碎普拉格雷片的比较）试验将疑似 STEMI 的患者随机分为救护车中给予普拉格雷 60mg 负荷剂量的压碎片或整片。在 4 个时间点进行药效学测量：抗血小板治疗前、pPCI 开始时和结束时以及研究治疗开始后 4 小时。主要终点是 pPCI 结束时的高血小板反应性。次要终点是血小板反应性状态对冠状动脉再灌注标志物的影响。
共纳入 441 例患者。压碎普拉格雷组 pPCI 结束时高血小板反应性的发生率降低近一半（压碎组 34.7% vs. 未压碎组 61.6%；比值比 [OR] = 0.33；95%置信区间 [CI] = 0.22 至 0.50；p < 0.01）。冠状动脉造影开始时血小板反应性 <150 P2Y 反应单位与梗死相关动脉 pPCI 前 3 级血栓溶解分级增加相关（OR：1.78；95% CI：1.08 至 2.94；p = 0.02），但与 ST 段缓解无关（OR：0.80；95% CI：0.48 至 1.34；p = 0.40）。
与整片普拉格雷相比，STEMI 患者行 pPCI 前口服压碎普拉格雷可显著改善急性期的血小板抑制作用。然而，仍有相当数量的患者在 pPCI 结束时仍存在血小板抑制不足，这表明需要替代药物来弥合血小板抑制方面的差距。
