Data_Sheet_2_Impact of Prasugrel and Ticagrelor on Platelet Reactivity in Patients With Acute Coronary Syndrome: A Meta-Analysis.pdf

BackgroundThis meta-analysis mainly aimed to compare the impact of prasugrel and ticagrelor on platelet reactivity (PR) in patients with acute coronary syndrome (ACS).MethodsWe 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.ResultsTwenty-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), P = 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 (P = 0.11) and VASP test (P = 0.20), and the incidence of HTPR within 2–6 h based on VN assay (P = 0.57) and within 24–48 h based on VN assay (P = 0.46) and VASP test (P = 0.72), the incidence of low on-treatment platelet reactivity (LTPR) within 6–18 h based on VASP test (P = 0.46) and 48 h based on VN assay (P = 0.97) and VASP test (P = 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), P < 0.00001]and VASP test [WMD = −9.10 (−13.88, −4.32), P = 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), P < 0.00001], the incidence of LTPR of ticagrelor was significantly higher than prasugrel based on VN assay [RR = 6.54 (4.21, 10.14), P < 0.00001] and VASP test [RR = 2.65 (1.78, 3.96), P < 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 (P = 0.86), cardiovascular death (P = 0.49), myocardial infarction (P = 0.67), stroke (P = 0.51), target vessel revascularization (P = 0.51), stent thrombosis (P = 0.90), TIMI major bleeding (P = 0.86) and bleeding BARC type ≥ 2 (P = 0.77). The risk of bleeding BARC type 1 of ticagrelor was significantly higher than prasugrel [RR = 1.44 (1.03, 2.02), P = 0.03].ConclusionsCompared 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.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022304205, identifier: CRD42022304205.

背景：本项荟萃分析主要旨在比较普拉格雷与替格瑞洛对急性冠脉综合征（ACS）患者血小板反应性（PR）的影响。方法：我们检索了四个电子数据库，以识别比较普拉格雷与替格瑞洛对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）]及LD效应时间进行了分组分析，并通过敏感性分析评估了结果的稳健性。结果：共有25项研究，涉及5,098名患者符合纳入标准。在LD后，基于血管舒张剂诱导的磷酸化蛋白（VASP）测试，替格瑞洛治疗期间高血小板反应性（HTPR）的发生率在6-18小时内显著低于普拉格雷[相对风险（RR）= 0.25（0.07，0.85），P = 0.03]，替格瑞洛与普拉格雷在以下结果中无显著差异：基于VerifyNow P2Y12（VN）测试的24-48小时血小板抑制作用（P = 0.11）和VASP测试（P = 0.20），以及基于VN测试的2-6小时和24-48小时HTPR发生率（P = 0.57）和基于VN测试的24-48小时及VASP测试的48小时HTPR发生率（P = 0.46），基于VASP测试的6-18小时低血小板反应性（LTPR）发生率（P = 0.46）和基于VN测试的48小时及VASP测试的48小时LTPR发生率（P = 0.97）。在MTD后，基于VN测试和VASP测试的血小板抑制作用，替格瑞洛强于普拉格雷[WMD = −41.64（−47.16，−36.11），P < 0.00001]和[WMD = −9.10（−13.88，−4.32），P = 0.0002]，基于VN测试的替格瑞洛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测试和VASP测试的替格瑞洛LTPR发生率显著高于普拉格雷[RR = 6.54（4.21，10.14），P < 0.00001]和[RR = 2.65（1.78，3.96），P < 0.00001]。多重电极聚集测量（MEA）测试的结果与另外两种检测方法在血小板抑制作用、HTPR和LTPR发生率方面不一致。在以下临床结果中，替格瑞洛与普拉格雷无显著差异：全因死亡率（P = 0.86）、心血管死亡率（P = 0.49）、心肌梗死（P = 0.67）、卒中（P = 0.51）、目标血管血运重建（P = 0.51）、支架血栓形成（P = 0.90）、TIMI主要出血（P = 0.86）和出血BARC类型≥2（P = 0.77）。替格瑞洛出血BARC类型1的风险显著高于普拉格雷[RR = 1.44（1.03，2.02），P = 0.03]。结论：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和出血BARC类型1发生率较高，而在血栓/缺血、出血BARC类型≥2和TIMI主要出血风险方面可能没有显著差异。LTPR发生率较高可能表明出血BARC类型1的风险较高。VN测试的结果与VASP测试一致，而非MEA测试。系统评价注册：https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022304205，标识符：CRD42022304205。