High On-Treatment Platelet Reactivity After Prasugrel Loading Dose and Cardiovascular Events After Percutaneous Coronary Intervention in Acute Coronary Syndromes

Bonello, Laurent; Pansiéri, Michel; Mancini, Julien; Bonello, R; Maillard, Luc; Barnay, Pierre; Rossi, P; Aitmokhtar, Omar; Jouve, Bernard; Collet, F; Peyre, Jean-Pascal; Wittenberg, Olivier; Labriolle, Axel de; Camilleri, Élise; Cheneau, Édouard; Cabassome, Elma; Dignat-George, Françoise; Camoin-Jau, Laurence; Paganelli, Franck

doi:10.1016/j.jacc.2011.04.017

Cited by 196 publications

(121 citation statements)

References 17 publications

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“…Similarly, we expected that additional administration of 30 mg of prasugrel in HTPR patients who had received a 600 mg loading dose of clopidogrel would decrease PRI to a value comparable with that observed in clopidogrel-naive patients after treatment with a 60 mg loading dose of prasugrel (34.3 ± 23.1%) [19]. Additionally, we anticipated in our prasugrel-treated patients to obtain PRI values at 30 days comparable to these observed in the TRITON-TIMI 38 platelet substudy at this time point (33.6 ± 2.9%) [20].…”

Section: Statistical Analysis and Sample Size Calculationmentioning

confidence: 74%

“…However, recent studies indicated that the phenomenon of HTPR also refers to subjects treated with prasugrel [20,21]. The prevalence of HTPR defined as the PRI value ≥ 50% measured 6-12 h after the administration of a 60 mg loading dose of prasugrel among 301 ACS patients successfully treated with PCI in a multicenter French study was 25.2% [19]. This rate corresponds with the prevalence of HTPR on prasugrel at 30 days in the TRITON-TIMI 38 platelet substudy (24% among 51 patients) [20], based on the same definition as applied by Bonello et al [19].…”

Section: Discussionmentioning

confidence: 99%

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Prasugrel overcomes high on-clopidogrel platelet reactivity in the acute phase of acute coronary syndrome and maintains its antiplatelet potency at 30-day follow-up

et al. 2014

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Background: The aim of this study was to assess antiplatelet effect of prasugrel in acute coronary syndrome (ACS) patients with high on-treatment platelet reactivity (HTPR) on clopidogrel, undergoing percutaneous coronary intervention (PCI).Methods : A prospective, platelet reactivity-guided, parallel-group, open-label (70.0 [61.3--75.6] vs. 11.9 [6.8-25.7]%; p < 0.000001) and slightly but significantly rose between 24 h and 30 days (27.9 [15.5-46.8 24 h (25.1 [13.7-40.2] vs. 22.0 [18.4-36.8 (30.3 [20.4-45.7 (Cardiol J 2014; 21, 5: 547-556) ]%; p < 0.0006). In contrast, median PRI values in the clopidogrel group were similar at baseline and at ]%; p = NS) and then modestly rose at 30 days

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Section: Statistical Analysis and Sample Size Calculationmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Prasugrel overcomes high on-clopidogrel platelet reactivity in the acute phase of acute coronary syndrome and maintains its antiplatelet potency at 30-day follow-up

et al. 2014

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“…According to an earlier trial, more than half of the STEMI patients treated with LD of integral ticagrelor still have HRPR up to 4 hours after administration of the drug. (7) Given the fact that suboptimal platelet inhibition is an important predictor of ischemic complications, such as stent thrombosis, (19) there is a time window after primary PCI, in which patients are at increased risk for ischemic complications.…”

Section: Discussionmentioning

confidence: 99%

Chewed ticagrelor tablets provide faster platelet inhibition compared to integral tablets

Venetsanos

Lawesson

Swahn

et al. 2017

Thrombosis Research

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Chewed ticagrelor tablets provide faster platelet inhibition compared to integral tablets: The inhibition of platelet aggregation after administration of three different ticagrelor formulations (IPAADTica) study, a randomised controlled trial., Thrombosis Research, 2017. 149, pp.88-94 MethodsNinety nine patients with stable angina were randomly assigned, in a 3:1:1 fashion, to one of the following 180 mg ticagrelor loading dose (LD) formulations: A) Integral B) Crushed or C) Chewed tablets. Platelet reactivity (PR) was assessed with VerifyNow before, 20 and 60 minutes after LD. High Residual platelet reactivity (HRPR) was defined as > 208 P2Y12 reaction units (PRU). ResultsThere was no significant difference in PRU values at baseline. PRU 20 minutes after LD were 237 (182 -295), 112 (53 -238) and 84 (29 -129) and 60 minutes after LD, 56 (15 -150), 51 (18 -85) and 9 (7 -34) in integral, crushed and chewed ticagrelor LD, respectively (p<0.01 for both). Chewed ticagrelor tablets resulted in significantly lower PRU values compared to crushed or integral tablets at 20 and 60 minutes. Crushed ticagrelor LD resulted in significantly lower PRU values compared to integral tablets at 20 minutes whereas no difference was observed at 60 minutes.At 20 minutes, no patients had HRPR with chewed ticagrelor compared to 68% with integral and 30% with crushed ticagrelor LD (p<0.01). ConclusionWith crushed or chewed ticagrelor tablets a more rapid platelet inhibition may be achieved, compared to standard integral tablets. We also show that administration of chewed tablets is feasible and provides faster inhibition than either crushed or integral tablets. CLINICAL TRIAL REGISTRATION:European Clinical Trial Database (EudraCT number 2014-002227-96).

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“…Likewise, Valgimgli et al17 reported that treatment with tirofiban, in patients who had HPR with clopidogrel, resulted in a 40% reduction in the incidence of PMI compared with clopidogrel. Although it has been assumed that the use of potent P2Y 12 inhibitors would overcome the problem of HPR, recent data4 showed that HPR was still observed in a significant number of patients (25.2%) with prasugrel, a potent P2Y 12 inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Ticagrelor and Eptifibatide Bolus Versus Ticagrelor and Eptifibatide Bolus With 2‐Hour Infusion in High‐Risk Acute Coronary Syndromes Patients Undergoing Early Percutaneous Coronary Intervention

Marian

Alli

Solaiman

et al. 2017

JAHA

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BackgroundIn patients with non‐ST‐segment elevation acute coronary syndromes, inhibition of platelet aggregation (IPA) with a potent P2Y12 inhibitor, ticagrelor, was inferior to tirofiban infusion at 2 hours, indicating that glycoprotein IIb/IIIa inhibitors are still needed. Ticagrelor and eptifibatide bolus only may maximally inhibit platelet aggregation and decrease bleeding, but IPA with ticagrelor and eptifibatide bolus versus 2‐hour infusion is unknown.Methods and ResultsA total of 70 P2Y12‐naïve patients, with high‐risk non‐ST‐segment elevation acute coronary syndromes, were randomized to ticagrelor and eptifibatide bolus (group 1) versus ticagrelor and eptifibatide bolus with 2‐hour infusion (group 2). Levels of IPA with ADP, thrombin receptor‐activating peptide, collagen, and high on‐treatment platelet reactivity were measured by light transmission aggregometry at baseline and at 2, 6, and 24 hours after percutaneous coronary intervention in both groups. The primary end point, IPA with ADP 20 μmol/L at 2 hours, was 99.59±0.43% in group 1 versus 99.88±1.0% in group 2 (P<0.001 for noninferiority). High on‐treatment platelet reactivity with ADP was zero at 2, 6, and 24 hours in both groups. IPA levels with ADP, thrombin receptor‐activating peptide, and collagen were significantly higher at 2 and 6 hours than at 24 hours in both groups. Periprocedural myocardial infarction was not significantly different between the groups. Hemoglobin level was significantly less at 24 hours versus baseline in group 2 (13.35±1.8 versus 12.38±1.8 g/dL, respectively; P<0.01).ConclusionsTicagrelor and eptifibatide bolus maximally inhibited platelet aggregation at 2 hours, which was associated with no significant hemoglobin drop after percutaneous coronary intervention. This obviates the need for eptifibatide 2‐hour infusion and might decrease bleeding complications.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01919723.

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High On-Treatment Platelet Reactivity After Prasugrel Loading Dose and Cardiovascular Events After Percutaneous Coronary Intervention in Acute Coronary Syndromes

Abstract: Despite the use of prasugrel, a significant number of patients undergoing PCI in the setting of acute coronary syndromes do not achieve optimal PR inhibition. Such patients have a higher risk for MACE after PCI.

Cited by 196 publications

References 17 publications

Prasugrel overcomes high on-clopidogrel platelet reactivity in the acute phase of acute coronary syndrome and maintains its antiplatelet potency at 30-day follow-up

Prasugrel overcomes high on-clopidogrel platelet reactivity in the acute phase of acute coronary syndrome and maintains its antiplatelet potency at 30-day follow-up

Chewed ticagrelor tablets provide faster platelet inhibition compared to integral tablets

Ticagrelor and Eptifibatide Bolus Versus Ticagrelor and Eptifibatide Bolus With 2‐Hour Infusion in High‐Risk Acute Coronary Syndromes Patients Undergoing Early Percutaneous Coronary Intervention

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