Inhibitory Effects of Ticagrelor Compared With Clopidogrel on Platelet Function in Patients With Acute Coronary Syndromes

Storey, Robert F.; Angiolillo, Dominick J.; Patil, Satish G; Desai, Bhaloo; Ecob, Rosemary; Husted, Steen; Emanuelsson, Håkan; Cannon, Christopher P.; Becker, Richard C.; Wallentin, Lars

doi:10.1016/j.jacc.2010.03.100

Cited by 357 publications

(248 citation statements)

References 8 publications

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“…We would like to underline that concomitant clopidogrel and antidiabetic drug use may significantly reduce therapeutic effect of clopidogrel. Ticagrelor is known for its fast onset [26], and has been shown to have greater antiplatelet activity compared with clopidogrel [27]. The PLATO study showed that ticagrelor is a more effective drug for the [2].…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…The differences in baseline characteristics were somewhat unexpected, as the drugs do not greatly differ from each other in terms of platelet inhibition. With the current approved maintenance dosing for both drugs, adequate levels of platelet inhibition 18 are achieved in over 90% of patients 11, 17, 19, 20, 21, 22.…”

Section: Discussionmentioning

confidence: 99%

“Real‐World” Comparison of Prasugrel With Ticagrelor in Patients With Acute Coronary Syndrome Treated With Percutaneous Coronary Intervention in the United States

Larmore

Effron

Molife

et al. 2015

Cathet Cardio Intervent

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ObjectivesThe 30‐day clinical outcomes with prasugrel or ticagrelor were compared using a US payer database in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).BackgroundPrasugrel and ticagrelor demonstrated superior efficacy with increased non‐coronary artery bypass graft major bleeding compared with clopidogrel in randomized clinical trials. No direct randomized or observational studies have compared clinical outcomes between prasugrel and ticagrelor.MethodsPatients hospitalized for ACS‐PCI between August 1, 2011 and April 30, 2013 and prescribed prasugrel or ticagrelor were selected. Drug treatment cohorts were propensity matched based upon demographic and clinical characteristics. The primary objective compared 30‐day net adverse clinical events (NACE) in prasugrel‐ and ticagrelor‐treated patients using a prespecified 20% noninferiority margin. Secondary objectives included comparisons of major adverse cardiovascular events (MACE) and major bleeding.ResultsData were available for 16,098 patients (prasugrel, n = 13,134; ticagrelor, n = 2,964). In unmatched cohorts, prasugrel‐treated patients were younger with fewer comorbidities than ticagrelor‐treated patients, and 30‐day NACE rates were 5.6 and 9.3%, respectively (P < 0.001). Following propensity matching, NACE was noninferior (P < 0.001) and 22% lower in prasugrel‐treated than in ticagrelor‐treated patients (RR, 0.78; 95% CI, 0.64–0.94). A 30‐day adjusted MACE (RR, 0.80; 95% CI, 0.64–0.98) and major bleeding (RR, 0.65; 95% CI, 0.45–0.95) were also lower in prasugrel‐treated patients compared with ticagrelor‐treated patients.ConclusionsIn this “real‐world,” retrospective, observational study, physicians appear to preferentially use prasugrel in younger patients with lower risk of bleeding or comorbidities compared with ticagrelor. Following adjustment, clinical outcomes associated with prasugrel use appear as good, if not better, than those associated with ticagrelor in ACS‐PCI patients. © 2015 Wiley Periodicals, Inc.

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“…Более благоприятные клинические исходы при на-значении прасугрела или тикагрелора в сравнении с клопидогрелом у пациентов с ОКС с выполненным ЧКВ были убедительно продемонстрированы в 2 круп-ных рандомизированных клинических исследованиях (РКИ), соответственно TRITON-TIMI 38 и PLATO [20,21]. Их результаты стали основой для одобрения при-менения прасугрела и тикагрелора у этой категории больных в разных странах мира и включения их в ос-новные международные и российские рекомендации по лечению ОКС.…”

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“…Полученные в исследованиях TRITON-TIMI 38 и PLATO результаты по эффективности и безопасности прасугрела и тикагрелора крайне сложно сопоставлять между собой, так как существовали определенные раз-личия в популяции включенных пациентов и в дизайне исследований [20][21][22]. Терапия новыми блокаторами P2Y12-рецепторов в составе ДАТ ассоциировалась в обоих РКИ с лучшими клиническими исходами по сравнению с клопидогрелом.…”

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“…По данным РКИ, в связи с более высокими рисками кровотечений и отсутствием клинических преимуществ в отдельных подгруппах прасугрел не может быть рекомендован пациенту с инсультом или транзиторной ишемической атакой в анамнезе [20][21][22][23]. Если после тщательной индивидуальной оценки отношения «польза-риск» принимается решение в пользу назначения препарата пациенту старше 75 лет или с малой массой тела, то поддерживающая доза препарата снижается в 2 раза [9].…”

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Antiplatelet Therapy of Acute Coronary Syndrome: Current Capab Ilities

Константинова¹,

Гиляров²,

Шостак³

et al. 2018

Klinicist

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Dual antiplatelet therapy (acetylsalicylic acid and platelet P2Y12 receptor antagonist) is a standard component of treatment of any type of acute coronary syndrome, independently of perfusion and the chosen treatment strategy. Due to certain limitations of clopidogrel as the 2nd component of dual antiplatelet therapy in patients with acute coronary syndrome and percutaneous coronary intervention, the possibility of using prasugrel or ticagrelor should be considered first. Their effectiveness is higher than clopidogrel’s, as was demonstrated in large clinical trials. As a result, prasugrel and ticagrelor were included in all major international and Russian guidelines on treatment of this category of patients with the same class and level of evidence. Currently, there’re no data from any finished large randomized clinical trials of sufficient statistical power directly comparing the effectiveness and safety of prasugrel and ticagrelor. Therefore, careful analysis of the accumulated data on the safety and effectiveness of each drug including meta-analyses and registries is necessary for providing the best care for every individual patient.

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Inhibitory Effects of Ticagrelor Compared With Clopidogrel on Platelet Function in Patients With Acute Coronary Syndromes

Abstract: Ticagrelor achieves greater antiplatelet effect than clopidogrel in patients with acute coronary syndromes, both in the first hours of treatment and during maintenance therapy.

Cited by 357 publications

References 8 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

“Real‐World” Comparison of Prasugrel With Ticagrelor in Patients With Acute Coronary Syndrome Treated With Percutaneous Coronary Intervention in the United States

Antiplatelet Therapy of Acute Coronary Syndrome: Current Capab Ilities

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