Dai Lulu, Xu Jiawei, Jiang Yuerong, Chen Keji
National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Graduate School of Beijing University of Chinese Medicine, Beijing, China.
Front Cardiovasc Med. 2022 Jun 9;9:905607. doi: 10.3389/fcvm.2022.905607. eCollection 2022.
This meta-analysis mainly aimed to compare the impact of prasugrel and ticagrelor on platelet reactivity (PR) in patients with acute coronary syndrome (ACS).
We searched four electronic databases to identify randomized controlled trials and cohort studies comparing the impact of prasugrel and ticagrelor on PR in patients with ACS. We performed group analyses according to three detection methods, drug dose [loading dose (LD) and maintenance dose (MTD)] and LD effect time, and assessed the robustness of the results through sensitivity analysis.
Twenty-five studies with 5,098 patients were eligible. After LD, the incidence of high on-treatment platelet reactivity (HTPR) of ticagrelor was significantly lower than that of prasugrel within 6-18 h based on vasodilator-stimulated phosphoprotein (VASP) test [RR = 0.25 (0.07, 0.85), = 0.03], there was no significant difference between ticagrelor and prasugrel in the following results: platelets inhibitory effect within 24-48 h based on VerifyNow P2Y12 (VN) assay ( = 0.11) and VASP test ( = 0.20), and the incidence of HTPR within 2-6 h based on VN assay ( = 0.57) and within 24-48 h based on VN assay ( = 0.46) and VASP test ( = 0.72), the incidence of low on-treatment platelet reactivity (LTPR) within 6-18 h based on VASP test ( = 0.46) and 48 h based on VN assay ( = 0.97) and VASP test ( = 0.73). After MTD, the platelet inhibitory effect of ticagrelor was stronger than that of prasugrel based on VN assay [WMD = -41.64 (-47.16, -36.11), < 0.00001]and VASP test [WMD = -9.10 (-13.88, -4.32), = 0.0002], the incidence of HTPR of ticagrelor was significantly lower than that of prasugrel based on VN assay [RR = 0.05 (0.02, 0.16), < 0.00001], the incidence of LTPR of ticagrelor was significantly higher than prasugrel based on VN assay [RR = 6.54 (4.21, 10.14), < 0.00001] and VASP test [RR = 2.65 (1.78, 3.96), < 0.00001], the results of Multiple Electrode Aggregometry (MEA) test was inconsistent with the other two detection methods in platelet inhibitory effect and the incidence of HTPR and LTPR. There was no significant difference between ticagrelor and prasugrel in the following clinical outcomes: all-cause death ( = 0.86), cardiovascular death ( = 0.49), myocardial infarction ( = 0.67), stroke ( = 0.51), target vessel revascularization ( = 0.51), stent thrombosis ( = 0.90), TIMI major bleeding ( = 0.86) and bleeding BARC type ≥ 2 ( = 0.77). The risk of bleeding BARC type 1 of ticagrelor was significantly higher than prasugrel [RR = 1.44 (1.03, 2.02), = 0.03].
Compared with prasugrel, ticagrelor might have a stronger platelet inhibition effect, with a lower incidence of HTPR and a higher incidence of LTPR and bleeding BARC type 1, while there might be no significant difference in the risk of thrombosis/ischemic, bleeding BARC Type ≥ 2 and TIMI major bleeding. A higher incidence of LTPR might indicate a higher risk of bleeding BARC type 1. The results of VN assay were consistent with that of VASP test, and not with the MEA test.
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022304205, identifier: CRD42022304205.
本荟萃分析主要旨在比较普拉格雷和替格瑞洛对急性冠状动脉综合征（ACS）患者血小板反应性（PR）的影响。
我们检索了四个电子数据库，以确定比较普拉格雷和替格瑞洛对ACS患者PR影响的随机对照试验和队列研究。我们根据三种检测方法、药物剂量[负荷剂量（LD）和维持剂量（MTD）]以及LD效应时间进行分组分析，并通过敏感性分析评估结果的稳健性。
25项研究共5098例患者符合纳入标准。负荷剂量后，基于血管扩张剂刺激的磷蛋白（VASP）试验，替格瑞洛在6 - 18小时内的高治疗期血小板反应性（HTPR）发生率显著低于普拉格雷[RR = 0.25（0.07，0.85），P = 0.03]，在以下结果中替格瑞洛与普拉格雷之间无显著差异：基于VerifyNow P2Y12（VN）分析在24 - 48小时内的血小板抑制作用（P = 0.11）和VASP试验（P = 0.20），以及基于VN分析在2 - 6小时内（P = 0.57）和基于VN分析在24 - 48小时内（P = 0.46）和VASP试验（P = 0.72）的HTPR发生率，基于VASP试验在6 - 18小时内（P = 0.46）和基于VN分析在48小时内（P = 0.97）和VASP试验（P = 0.73）的低治疗期血小板反应性（LTPR）发生率。维持剂量后，基于VN分析[WMD = -41.64（-47.16，-36.11），P < 0.00001]和VASP试验[WMD = -9.10（-13.88，-4.32），P = 0.0002]，替格瑞洛的血小板抑制作用强于普拉格雷，基于VN分析替格瑞洛的HTPR发生率显著低于普拉格雷[RR = 0.05（0.02，0.16），P < 0.00001]，基于VN分析替格瑞洛的LTPR发生率显著高于普拉格雷[RR = 6.54（4.21，10.14），P < 0.00001]和VASP试验[RR = 2.65（1.78，3.96），P < 0.00001]，多电极聚集测定（MEA）试验在血小板抑制作用以及HTPR和LTPR发生率方面的结果与其他两种检测方法不一致。替格瑞洛和普拉格雷在以下临床结局方面无显著差异：全因死亡（P = 0.86）、心血管死亡（P = 0.49）、心肌梗死（P = 0.67）、卒中（P = 0.51）、靶血管血运重建（P = 0.51）、支架血栓形成（P = 0.90）、TIMI大出血（P = 0.86）和BARC≥2型出血（P = 0.77）。替格瑞洛的BARC 1型出血风险显著高于普拉格雷[RR = 1.44（1.03，2.02），P = 0.03]。
与普拉格雷相比，替格瑞洛可能具有更强的血小板抑制作用，HTPR发生率较低，LTPR发生率和BARC 1型出血发生率较高，而在血栓形成/缺血风险、BARC≥2型出血和TIMI大出血方面可能无显著差异。较高的LTPR发生率可能表明BARC 1型出血风险较高。VN分析结果与VASP试验结果一致，与MEA试验结果不一致。
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022304205，标识符：CRD42022304205 。
