Platelet reactivity during ticagrelor maintenance therapy: A patient-level data meta-analysis

Alexopoulos, Dimitrios; Xanthopoulou, Ioanna; Storey, Robert F.; Bliden, Kevin P.; Tantry, Udaya S.; Angiolillo, Dominick J.; Gurbel, Paul A.

doi:10.1016/j.ahj.2014.06.026

Cited by 49 publications

(36 citation statements)

References 33 publications

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“…Alexopoulos et al suggest that diabetes mellitus and older age of a patient (older than 70 years) during clopidogrel therapy might be associated with higher platelet reactivity [38]. However, patient age and diabetes had no significant antiplatelet effect in our patient group treated with ticagrelor.…”

Section: Discussioncontrasting

confidence: 49%

The Impact of Clinical and Genetic Factors on Ticagrelor and Clopidogrel Antiplatelet Therapy

et al. 2017

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Aim: To determine clinically significant factors which may alter the effect of dual antiplatelet therapy with aspirin and ticagrelor or clopidogrel in patients who had undergone percutaneous coronary intervention and stent implantation. Materials & methods: The study included 378 patients. All the patients had undergone percutaneous coronary intervention and stent implantation. Platelet aggregation and genotyping for CYP2C19 *2 (rs4244285) and CYP4F2 (rs2108622, rs1558139, rs3093135 and rs2074902) was performed. Results: Significantly lower platelet aggregation values (% agr ) were detected in ticagrelor users who carried CYP4F2 rs3093135 TT variant (14.67 ± 5.07% agr ) versus AA (22.88 ± 6.30% agr ), p = 0.0004, or AT (20.56 ± 6.51% agr ), p = 0.0126. Conclusion: Results of the current study showed that CYP4F2 rs3093135 TT variant carriers had a higher antiplatelet effect of ticagrelor, and more frequently had nonprocedural bleeding during ticagrelor therapy, as compared with AA and AT variant carriers. Dual antiplatelet therapy (DAPT) with aspirin and ADP receptor blocker (ticagrelor, prasugrel or clopidogrel) is recommended for the secondary prevention of ischemic complications in patients with acute coronary syndromes, following percutaneous coronary intervention (PCI) and stent implantation. In large trials, prasugrel and ticagrelor have showed superior therapeutic effect compared with clopidogrel. Prasugrel reduced primary end point (cardiovascular death, nonfatal myocardial infarction (MI) or stroke) in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitionThrombolysis In Myocardial Infarction 38 [1]. Ticagrelor was shown to reduce primary end point in the Platelet Inhibition and Patient Outcomes (PLATO) trial [2]. Thus, the European Society of Cardiology issued guidelines for the diagnosis and treatment of ST-elevation myocardial infarction (STEMI) [3], non-STEMI (NSTEMI) [4] and myocardial revascularization [5]. According to these guidelines, ticagrelor or prasugrel is now preferred over clopidogrel due to their increased antiplatelet activity and lower risk of vascular thrombotic events. However, ticagrelor or prasugrel may cause higher incidence of nonprocedural noncoronary artery bypass grafting bleeding [1,2,6].Clopidogrel, a key antagonist of platelet ADP receptors, has been in use over the past two decades. This prodrug is metabolized by two main competing pathways. The major one is via human hepatic carboxylesterase 1, which hydrolyze clopidogrel into inactive clopidogrel acid metabolite. The minor one consists of two CYP450-dependent steps [7,8]. During the first step, clopidogrel is metabolized into a thiolactone (2-oxo-clopidogrel) by CYP1A2, CYP2B6 and CYP2C19. The second step involves CYP2B6, CYP2C9, CYP2C19 and CYP3A4, which forms active thiol-containing metabolite [7]. In total,

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Section: Discussioncontrasting

confidence: 49%

The Impact of Clinical and Genetic Factors on Ticagrelor and Clopidogrel Antiplatelet Therapy

et al. 2017

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“…22 In 26 STEMI patients reported previously and included in this study, baseline platelet reactivity predicted platelet reactivity 2 h after ticagrelor LD, while in a large cohort of patients under ticagrelor maintenance dose, BASE (measured by VerifyNow), predicted platelet reactivity, although with a very low effect size. 23, 24 In line with the aforementioned reports, in an exclusively STEMI cohort described in the present study and treated with any of the 3 oral antiplatelet agents, pre-treatment platelet reactivity was positively associated with platelet reactivity 2 h after LD.…”

Section: Discussionsupporting

confidence: 78%

“…[24][25][26] In the present analysis involving the early phase of STEMI, a similar positive association between increasing BMI and platelet reactivity 2 h after LD was identified. Morphine use was also positively associated with platelet reactivity 2 h after LD, in accordance with previous studies, most likely by delaying antiplatelet agent absorption.…”

Section: Discussionsupporting

confidence: 59%

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Factors Affecting Platelet Reactivity 2 Hours After P2Y<sub>12</sub> Receptor Antagonist Loading in Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction　– Impact of Pain-to-Loading Time –

Xanthopoulou¹,

Davlouros²,

Tsigkas³

et al. 2016

Circ J

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“…Ideal strategies for P2Y 12 inhibition would achieve an optimal level of P2Y 12 inhibition that maximizes reductions in risk of adverse cardiovascular events without an excessive increase in risk of bleeding. Ticagrelor maintenance therapy achieves a very high level of P2Y 12 inhibition [27,29], so aiming for a higher level than this is not necessary or desirable since this may only result in increases in bleeding that outweigh potential cardiovascular benefits. It is therefore unlikely that future strategies of P2Y 12 inhibition will involve greater levels of P2Y 12 inhibition than current strategies, in the majority of patients at least.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

The future of P2Y₁₂ receptor antagonists

Thomas

Storey

2015

Platelets

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Platelet P2Y 12 inhibitors have become a central component of the treatment strategy for patients with atherothrombosis due to the importance of platelet P2Y 12 receptors in arterial thrombosis. P2Y 12 inhibitors effectively reduce the risk of adverse cardiovascular events in patients with acute coronary syndromes (ACS) and patients undergoing percutaneous coronary intervention (PCI). However, despite this, patients with ACS continue to suffer from recurrent atherothrombosis and an increased risk of mortality. In addition, P2Y 12 inhibitors increase the risk of bleeding, thereby limiting their clinical benefit. It is therefore clear that further optimizations are needed in the pharmacology and treatment strategies of P2Y 12 inhibitors. The objective of these optimizations is to maximize cardiovascular benefit whilst minimizing adverse effects on haemostasis. This review article summarizes the most successful recent strategies in P2Y 12 inhibition in order to identify the optimizations and developments that are most likely to be successful in the future.

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Platelet reactivity during ticagrelor maintenance therapy: A patient-level data meta-analysis

Cited by 49 publications

References 33 publications

The Impact of Clinical and Genetic Factors on Ticagrelor and Clopidogrel Antiplatelet Therapy

The Impact of Clinical and Genetic Factors on Ticagrelor and Clopidogrel Antiplatelet Therapy

Factors Affecting Platelet Reactivity 2 Hours After P2Y<sub>12</sub> Receptor Antagonist Loading in Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction　– Impact of Pain-to-Loading Time –

The future of P2Y₁₂ receptor antagonists

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Platelet reactivity during ticagrelor maintenance therapy: A patient-level data meta-analysis

Cited by 49 publications

References 33 publications

The Impact of Clinical and Genetic Factors on Ticagrelor and Clopidogrel Antiplatelet Therapy

The Impact of Clinical and Genetic Factors on Ticagrelor and Clopidogrel Antiplatelet Therapy

Factors Affecting Platelet Reactivity 2 Hours After P2Y<sub>12</sub> Receptor Antagonist Loading in Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction – Impact of Pain-to-Loading Time –

The future of P2Y12 receptor antagonists

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Factors Affecting Platelet Reactivity 2 Hours After P2Y<sub>12</sub> Receptor Antagonist Loading in Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction　– Impact of Pain-to-Loading Time –

The future of P2Y₁₂ receptor antagonists