Potent P2Y12 receptor inhibitors in patients with acute coronary syndrome

2013 ◽  
Vol 33 (01) ◽  
pp. 9-15 ◽  
Author(s):  
M. Orban ◽  
S. Massberg ◽  
D. Sibbing
Keyword(s):  
Acute Coronary Syndrome ◽  
Large Scale ◽  
Platelet Reactivity ◽  
Blood Platelets ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
P2y12 Receptor ◽  
Onset Of Action ◽  
Thrombotic Risk ◽  
Coronary Syndrome

SummaryBlood platelets are highly activated in the setting of an acute coronary syndrome (ACS). This fact mandates the need for potent platelet inhibition in ACS patients and especially in patients undergoing a percutaneous coronary intervention (PCI). The 2nd generation thienopyridine clopidogrel has been the standard of treatment in the past. Due to its pharmacological properties including a delayed onset of action, a large response variability and an insufficient antiplatelet action in some patients (low responsiveness or high on-treatment platelet reactivity), there was a need to develop, to study and to introduce more potent agents with a fast, reliable and potent antiplatelet action. With the 3rd generation thienopyridine prasugrel and with ticagrelor two potent agents for antiplatelet treatment of ACS patients are available now. Both drugs have demonstrated their superiority compared to clopidogrel in terms of thrombotic risk reduction in large-scale randomized trials. However, for these agents and in line with the expectations towards a more potent anti platelet treatment regimen, a higher risk for bleeding was observed for prasugrel and ticagrelor. Further on, the new anti platelet agents have their own and characteristic contraindications and numerous issues to be considered in clinical practice.This review aims to provide an overview on the state of the art P2Y12 receptor directed inhibition in ACS patients with a focus on patients undergoing a coronary stenting procedure.

Diurnal Variability of On-Treatment Platelet Reactivity in Clopidogrel versus Prasugrel Treated Acute Coronary Syndrome Patients: A Pre-Specified TROPICAL-ACS Sub-Study

2019 ◽  
Vol 119 (04) ◽  
pp. 660-667 ◽  
Author(s):  
Matthias Freynhofer ◽  
Ralph Hein-Rothweiler ◽  
Paul Haller ◽  
Daniel Aradi ◽  
Döme Dézsi ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Early Morning ◽  
Platelet Inhibition ◽  
Control Group ◽  
Diurnal Variability ◽  
Coronary Syndrome ◽  
Adp Receptor

AbstractLong-term evidence supports a clustering of cardiovascular events in the early morning and smaller mechanistic studies in aspirin-treated patients have shown increased platelet reactivity at the end of the dosing interval. Comparative pharmacodynamic analyses for different adenosine diphosphate (ADP) receptor inhibitors in percutaneous coronary intervention-treated acute coronary syndrome (ACS) patients are lacking and this pre-specified analysis from the randomized Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes (TROPICAL-ACS) trial aimed for the first time at investigating diurnal variability of on-treatment platelet reactivity in clopidogrel versus prasugrel treated patients. TROPICAL-ACS randomized 2,610 ACS patients to either treatment with prasugrel (control group) or to a platelet function testing-guided de-escalation of anti-platelet treatment with a switch to clopidogrel (guided de-escalation group). This study design enabled a diurnal comparison of on-prasugrel versus on-clopidogrel treatment platelet reactivity under steady-state conditions. For 2,526 patients (97%), both the exact time of blood sampling and the ADP-induced platelet aggregation value (in units, Multiplate analyser) were available. Platelet reactivity in patients on clopidogrel (n = 1,265) was higher and subject to significant diurnal variability (p = 0.019) with a peaking of platelet reactivity in the early morning (5–10 a.m.). In prasugrel-treated patients (n = 1,261), there was no sign for diurnal variability (p = 0.174) or a peaking of platelet reactivity in the morning. The potent ADP receptor inhibitor prasugrel is not subject to diurnal variability while we observed a significant diurnal variability of on-clopidogrel platelet reactivity. The clinical impact of this observation may differ for patients with and without an adequate response to clopidogrel treatment and the issue of diurnal variability of platelet reactivity in ACS patients warrants further investigation.

scholarly journals Validation of a New ELISA-Based Vasodilator-Associated Stimulated Phosphoprotein Phosphorylation Assay to Assess Platelet Reactivity Index in a Chinese Population

2017 ◽  
Vol 24 (3) ◽  
pp. 452-461 ◽  
Author(s):  
Peng Ding ◽  
Yujie Wei ◽  
Nana Chen ◽  
Huiliang Liu
Keyword(s):  
Acute Coronary Syndrome ◽  
Healthy Volunteers ◽  
Chinese Population ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Reactivity Index ◽  
Enzyme Linked Immunosorbent Assay ◽  
Coronary Syndrome

The level of platelet reactivity during P2Y12-adenosine diphosphate receptor antagonist is associated with ischemic and bleeding risks following percutaneous coronary intervention in acute coronary syndrome. Determining platelet reactivity inhibition may be valuable for confirming effective platelet inhibition for individual patients and identifying patients at risk of bleeding. The enzyme-linked immunosorbent assay (ELISA)-based vasodilator-stimulated phosphoprotein (VASP) assay offers unique advantages over other methods and has not been used in the Chinese population. We enrolled 10 healthy volunteers and 54 patients with acute coronary syndrome. The volunteers received no treatment, and patients were administered a loading dose of clopidogrel or ticagrelor. The platelet reactivity index (PRI) was measured using flow cytometry (FC)-VASP and ELISA-VASP at baseline and 8-hour postloading dose. Blood samples of healthy volunteers and clopidogrel- or ticagrelor-treated patients were frozen and stored for 1, 2, and 4 weeks after initial activation. All frozen samples were tested using ELISA-VASP. The PRI assessed by FC-VASP and ELISA-VASP correlated well showing a high degree of consistency in identifying high or low on-treatment platelet reactivity. No significant time-dependent changes in PRI results were observed in frozen samples stored up to 4 weeks compared to nonfrozen samples. The PRI of ticagrelor-treated patients was lower than that of clopidogrel-treated patients. The ELISA-VASP effectively assesses the PRI, and results obtained from frozen specimens are unaffected by storage and shipment prior to assay. Ticagrelor was superior to clopidogrel in decreasing the PRI.

scholarly journals Impact of Intravenous P2Y12-Receptor Inhibition with Cangrelor in Patients Presenting with Acute Coronary Syndrome and Cardiogenic Shock – a Case Series

2017 ◽  
Vol 42 (4) ◽  
pp. 1336-1341 ◽  
Author(s):  
Michal Droppa ◽  
Oliver Borst ◽  
Dominik Rath ◽  
Karin Müller ◽  
Meinrad Gawaz ◽  
...  
Keyword(s):  
Cardiogenic Shock ◽  
Platelet Reactivity ◽  
Case Series ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
P2y12 Receptor ◽  
Cardiac Events ◽  
Coronary Syndrome ◽  
Multiple Electrode Aggregometry ◽  
Single Center Experience

Background/Aims: Patients with acute coronary syndromes (ACS) presenting with cardiogenic shock (CS) are at particular risk for death and adverse cardiac events. Impaired effects and absorption of oral P2Y12-receptor inhibitors due to decreased organ hypoperfusion or hypothermia and challenges regarding oral administration contribute to this risk. We report a single center experience regarding the use of intravenous P2Y12-receptor inhibitor cangrelor in patients with CS treated with percutaneous coronary intervention (PCI). Methods: Twelve patients with ACS and CS undergoing PCI, not pretreated with oral P2Y12-receptor inhibitors, were treated with cangrelor. Platelet inhibition was assessed by multiple electrode aggregometry (MEA) before and after PCI, immediately and 2 hours after stopping the cangrelor infusion. Results: Nine patients recovered from their cardiogenic shock, 3 patients died. Platelet reactivity decreased from 65.9 (SD 41.0) U before PCI to 15.8 (SD 10.8) U after PCI, 13.4 (SD 7.7) U at the end of infusion and 33.8 (SD 19.9) 2 hours after stopping the cangrelor infusion. There was no non-responder under cangrelor infusion (MEA < 46 U). Conclusions: Due to its favorable PK/PD profile, cangrelor overcomes problems with reduced absorption and effects of oral P2Y12-receptor inhibitors and should be considered for periprocedural treatment of patients with CS.

Antiplatelet Therapy Prasugrel: A Novel Platelet ADP P2Y12 Receptor Antagonist

2010 ◽  
Vol 16 (2) ◽  
pp. 170-176 ◽  
Author(s):  
Shaker A. Mousa ◽  
Walter P. Jeske ◽  
Jawed Fareed
Keyword(s):  
Large Scale ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Phase Iii ◽  
Platelet Response ◽  
Onset Of Action ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
P2y12 Receptor Antagonist

Novel adenosine diphosphate (ADP) P2Y12 antagonists, including prasugrel, ticagrelor, cangrelor and elinogrel, are in various phases of clinical development. These ADP P2Y12 antagonists have advantages over clopidogrel ranging from faster onset to greater and less variable inhibition of platelet function. Novel ADP P2Y12 antagonists are under investigation to determine whether their use can result in improved antiplatelet activity, faster onset of action, and/or greater antithrombotic effects than clopidogrel, without an unacceptable increase in hemorrhagic or other side effects. Prasugrel (CS-747; LY-640315), a novel third-generation oral thienopyridine, is a specific, irreversible antagonist of the platelet ADP P2Y12 receptor. Preclinical and early phase clinical studies have shown prasugrel to be characterized by more potent antiplatelet effects, lower interindividual variability in platelet response, and faster onset of activity compared to clopidogrel. Recent findings from large-scale phase III testing showed prasugrel to be more efficacious in preventing ischemic events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI); however, this is achieved at the expense of an increased risk of bleeding. Prasugrel provides more rapid and consistent platelet inhibition than clopidogrel.

scholarly journals Loading with Oral P2Y12 Receptor Inhibitors: To Crush or Not to Crush?

2019 ◽  
Vol 119 (07) ◽  
pp. 1037-1047 ◽  
Author(s):  
Dimitrios Alexopoulos ◽  
Stylianos Dragasis ◽  
Nikolaos Kafkas
Keyword(s):  
Coronary Intervention ◽  
Platelet Inhibition ◽  
P2y12 Receptor ◽  
Current Evidence ◽  
Onset Of Action ◽  
Future Expectations ◽  
Coronary Syndrome ◽  
Clinical Scenarios ◽  
Number Of Patients ◽  
Receptor Inhibitor

AbstractOral P2Y12 receptor inhibitors represent a mainstay treatment in patients with acute coronary syndrome and those undergoing percutaneous coronary intervention. In the setting of ST-elevation myocardial infarction, when early platelet inhibition is highly desirable, the onset of action of oral P2Y12 receptor inhibitors is, however, delayed, likely due to delayed drug absorption. Crushing the tablets, which are to be used for patient loading with an oral P2Y12 receptor inhibitor, has been shown to provide earlier platelet inhibition than standard, integral tablets administration. Chewed ticagrelor tablets may also result in a similar effect. Such findings should be interpreted with caution, mainly due to the small number of patients enrolled and the nature (pharmacodynamic/pharmacokinetic) of the respective studies. Furthermore, in patients with out-of-hospital cardiac arrest, who remain comatose, crushing tablets is commonly applied in clinical practice for platelet P2Y12 receptor inhibition. In this review, we focus on current evidence regarding the role of crushed P2Y12 receptor inhibitor pills, analyzing clinical scenarios where most of the promise exists along with future expectations from this type of formulation. Large randomized studies are needed to draw firm conclusions regarding the clinical benefit of ‘crushing’ over the usual ‘not-crushing’ practice.

A Prospective, Randomized, Open-Label, Blinded, Endpoint Study Exploring Platelet Response to Half-Dose Prasugrel and Ticagrelor in Patients with the Acute Coronary Syndrome: HOPE-TAILOR Study

Cardiology ◽  
2017 ◽  
Vol 138 (4) ◽  
pp. 201-206 ◽  
Author(s):  
Cai De Jin ◽  
Moo Hyun Kim ◽  
Junghee Bang ◽  
Victor Serebruany
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Reactivity ◽  
Academic Research ◽  
P2y12 Receptor ◽  
Drug Eluting Stent ◽  
Platelet Response ◽  
Open Label ◽  
Korean Patients ◽  
Coronary Syndrome ◽  
Half Dose

Background: The optimal dosing of novel oral P2Y12 receptor platelet inhibitors such as prasugrel or ticagrelor is unclear and especially challenging in East Asians. We hypothesize that half-dose prasugrel and ticagrelor may be sufficient for long-term maintenance management in Korean patients with the acute coronary syndrome (ACS) compared with conventional dosages. Design: HOPE-TAILOR (Half Dose of Prasugrel and Ticagrelor in Platelet Response after Acute Coronary Syndromes) is a prospective, randomized, open-label, blinded, endpoint (PROBE) single-center, clinical trial. A total of 100 patients with ACS undergoing drug-eluting stent implantation will be randomly assigned to prasugrel, ticagrelor, or clopidogrel, and the patients in each treatment group will receive 1-month therapy with 100 mg q.d. aspirin plus prasugrel 10 mg q.d., ticagrelor 90 mg b.i.d., or clopidogrel 75 mg q.d., followed by half-dose prasugrel 5 mg q.d. or ticagrelor 45 mg b.i.d. for maintenance treatment but without clopidogrel dose reduction. The primary endpoint will be optimal platelet reactivity 3 months after coronary intervention, defined by VerifyNow Analyzer (PRU: 85-208) and vasodilator-stimulated phosphoprotein P2Y12 flow cytometry assay (platelet reactivity indices: 16-50%). Clinical outcomes will also be assessed, including major efficacy (composite of cardiac death, nonfatal myocardial infarction, repeat revascularization, or stroke) and safety (bleeding ≥2 according to the Bleeding Academic Research Consortium). Conclusion: HOPE-TAILOR is a prospective, randomized, open-label, blinded, endpoint study to explore the efficacy and safety of novel P2Y12 receptor inhibitors administered orally at half the dose in Korean patients with ACS. The results will be available late in 2017.

scholarly journals Subanalysis of the AUGUSTUS trial

2020 ◽  
Vol 25 ◽  
pp. 4104
Author(s):  
T. V. Pavlova ◽  
P. D. Duplyakova ◽  
O. V. Shkaeva ◽  
S. P. Krivova
Keyword(s):  
Acute Coronary Syndrome ◽  
Large Scale ◽  
Coronary Intervention ◽  
The Novel ◽  
Actual Clinical Practice ◽  
Coronary Syndrome ◽  
Hospitalization Rates ◽  
Percutaneous Coronary ◽  
Artery Disease ◽  
European Society Of Cardiology

Comorbidity is a common feature of a modern patient. The combination of atrial fibrillation (AF) and various types of coronary artery disease is widespread in actual clinical practice. In such cases, additional pathophysiological mechanisms appear that worsen the clinical course and patient’s prognosis. The management of AF patients who have undergone acute coronary syndrome and/or percutaneous coronary intervention is a challenging problem, which can be solved by large-scale clinical trials. The AUGUSTUS randomized trial with a two-by-two factorial design proved that full-dose apixaban is superior in safety to the vitamin K antagonist warfarin, while not inferior in effectiveness. This pattern has been preserved in several important subanalysis on stent thrombosis, hospitalization rates, and conservative management of acute coronary syndrome. The obtained results are included in the novel European Society of Cardiology guidelines on AF.

scholarly journals Does Baseline On-treatment Platelet Reactivity Impact Long-term Prognosis in Patients with Acute Coronary Syndrome and Thrombocytopenia Who Underwent Percutaneous Coronary Intervention?

2021 ◽  
Author(s):  
Ru Liu ◽  
Tianyu Li ◽  
Deshan Yuan ◽  
Yan Chen ◽  
Xiaofang Tang ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Acute Coronary Syndrome ◽  
Real World ◽  
Cox Regression ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
The Real ◽  
Coronary Syndrome ◽  
Percutaneous Coronary

Abstract Objectives: This study analyzed the association between on-treatment platelet reactivity and long-term outcomes of patients with acute coronary syndrome (ACS) and thrombocytopenia (TP) in the real world. Methods: A total of 10724 consecutive cases with coronary artery disease who underwent percutaneous coronary intervention (PCI) were collected from January to December 2013. Cases with ACS and TP under dual anti-platelet therapy were enrolled from the total cohort. 5-year clinical outcomes were evaluated among cases with high on-treatment platelet reactivity (HTPR), low on-treatment platelet reactivity (LTPR) and normal on-treatment platelet reactivity (NTPR), tested by thromboelastogram (TEG) at baseline. Results: Cases with HTPR, LTPR and NTPR accounted for 26.2%, 34.4% and 39.5%, respectively. Cases with HTPR were presented with the most male sex, lowest hemoglobin level, highest erythrocyte sedimentation rate and most LM or three-vessel disease, compared with the other two groups. The rates of 5-year all-cause death, major adverse cardiovascular and cerebrovascular events (MACCE), cardiac death, myocardial infarction (MI), revascularization, stroke and bleeding were all not significantly different among three groups. Multivariable Cox regression indicated that, compared with cases with NTPR, cases with HTPR were not independently associated with all endpoints, as well as cases with LTPR (all P>0.05). Conclusions: In patients with ACS and TP undergoing PCI, 5-year all-cause death, MACCE, MI, revascularization, stroke and bleeding risk were all similar between cases with HTPR and cases with NTPR, tested by TEG at baseline, in the real world. The comparison result was the same between cases with LTPR and NTPR.

On-ticagrelor platelet reactivity and clinical outcome in patients undergoing percutaneous coronary intervention for acute coronary syndrome

2020 ◽  
Author(s):  
marc laine ◽  
Vassili PANAGIDES ◽  
Corinne Frère ◽  
thomas cuisset ◽  
Caroline Gouarne ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Percutaneous Coronary Intervention ◽  
Acute Coronary Syndrome ◽  
Clinical Outcome ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Coronary Syndrome ◽  
Percutaneous Coronary ◽  
The Relationship

Background: A strong association between on-thienopyridines platelet reactivity (PR) and the risk of both thrombotic and bleeding events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) has been demonstrated. However, no study has analyzed the relationship between on-ticagrelor PR and clinical outcome in this clinical setting. Objectives: We aimed to investigate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein (VASP) index, and clinical outcome in patients with ACS undergoing PCI. Methods: We performed a prospective, multicenter, observational study of patients undergoing PCI for ACS. PR was measured using the VASP index following ticagrelor loading dose. The primary study endpoint was the rate of Bleeding Academic Research Consortium (BARC) type ≥2 at 1 year. The key secondary endpoint was the rate of major cardiovascular events (MACE) defined as the composite of cardiovascular death, myocardial infarction and urgent revascularization. Results: We included 570 ACS patients, among whom 33.9% had ST-elevation myocardial infarction. BARC type ≥ 2 bleeding occurred in 10.9% and MACE in 13.8%. PR was not associated with BARC ≥ 2 or with MACE (p=0.12 and p=0.56, respectively). No relationship between PR and outcomes was observed, neither when PR was analyzed quantitatively nor qualitatively (low on-treatment PR (LTPR) vs no LTPR). Conclusion: On-ticagrelor PR measured by the VASP was not associated with bleeding or thrombotic events in ACS patients undergoing PCI. PR measured by the VASP should not be used as a surrogate endpoint in studies on ticagrelor.

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