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

Abstract

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.

Clopidogrel resistance and its relevance: Current concepts

“…[ 50 51 52 ] Four meta-analyses have shown that HTPR is lower with ticagrelor compared to prasugrel. [ 53 54 55 56 ] However, some studies suggest the variation is due to the type of PFT assay used rather than the effect of the drug per se. [ 57 58 59 ] However, the small SWAP-3 trial demonstrated that switching to ticagrelor from prasugrel leads to further platelet inhibition and lower PRU as early as 2 h after drug initiation.…”

Resistance on the Latest Oral and Intravenous P2Y12 ADP Receptor Blockers in Patients with Acute Coronary Syndromes: Fact or Myth?

“…In other studies, the range of ticagrelor HTPR after loading dose administration ranged from 1.5 to 60.2%, depending on studied patient population, method used for HTPR detection and timing of blood sampling [ 50 , 51 , 63 , 64 , 65 , 66 , 67 ]. Although Verdoia et al reported in their studies [ 54 , 68 , 69 ] 8.6 to 13.7% prevalence of ticagrelor HTPR on maintenance dosing (tested 30 to 90 days post drug loading), it seems that a longer duration of ticagrelor therapy probably achieves sufficient platelet inhibition in the majority of patients, as the majority of so-far published studies, including meta-analyses, reported very low rates (0.0–1.9%) of ticagrelor HTPR ( Table 3 ) on long-term therapy [ 49 , 52 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ]. This prevalence practically limits the occurrence of ticagrelor HTPR to occasional clinical cases.…”

Features of Platelet Hemostasis in Patients with Various Sensitivity to Anti-Platelet Therapy in Different Terms of Q-wave Myocardial Infarction

“…Что касается частоты встречаемости ВОРТ при приеме ингибиторов рецепторов P2RY12 тромбоцитов, то она зависит от вида назначаемого лекарственного средства. При назначении тикагрелора и прасугрела она встречается в 0-3% и 3-15% соответственно [5,16,17]. При назначении клопидогрела частота его низкой эффективности у пациентов с ОКС исходно была от 29,5% [18] до 40,7% [19], что даже несколько выше по сравнению с нашими данными (24,5%).…”