P2Y12 inhibitors

2009 ◽  
Vol 29 (04) ◽  
pp. 339-348 ◽  
Author(s):  
J.-P. Collet ◽  
G. Montalescot
Keyword(s):  
Coronary Intervention ◽  
Loss Of Function ◽  
Atherosclerotic Vascular Disease ◽  
Vascular Events ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
Optimal Balance ◽  
P2y12 Antagonists ◽  
Percutaneous Coronary ◽  
Proven Efficacy

SummaryThe P2Y12 receptor has proven to be a key target in the prevention of complications associated with atherosclerotic vascular disease especially in the context of acute coronary syndrome and percutaneous coronary intervention in addition to aspirin. Three generationsof thienopyridines, ticlopidine, clopidogrel, and prasugrel have proven efficacy in the prevention of ischemic vascular events but with increased bleeding. The concept of individualized tailored therapy has recently emerged with the discovery of the diminished effect of some thienopyridine among carriers of the loss-of-function cytochrome (CYP) P4502C19*2 variant. Non-thienopyridine P2Y12 antagonists have also recently demonstrated that these benefits are not limited to one class of agents or may be generalizable to reversible antagonists of this receptor. Future rational use of these agents will require attention to disease and patient features to strike the optimal balance of benefit to risk.

scholarly journals De-Escalation of Antiplatelet Treatment in Patients with Myocardial Infarction Who Underwent Percutaneous Coronary Intervention: A Review of the Current Literature

2020 ◽  
Vol 9 (9) ◽  
pp. 2983 ◽  
Author(s):  
Daniel MF Claassens ◽  
Dirk Sibbing
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Bleeding Complication ◽  
Thrombotic Event ◽  
Coronary Intervention ◽  
Antiplatelet Treatment ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
Percutaneous Coronary ◽  
Event Rates ◽  
Function Testing

In acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI), treatment with the P2Y12 inhibitors ticagrelor or prasugrel is recommended over clopidogrel due to a better efficacy, albeit having more bleeding complication. These higher bleeding rates have provoked trials investigating de-escalation from ticagrelor or prasugrel to clopidogrel in the hope of reducing bleeding without increasing thrombotic event rates. In this review, we sought to present an overview of the major trials investigating several different options for de-escalation; unguided, platelet function testing- and genotype-guided. Based on these results, and on other established literature sources, such as guidelines and expert consensus papers, we provide an overview to help decide when and how to de-escalate antiplatelet therapy in ACS patients undergoing PCI.

Impact of clopidogrel and potent P2Y12-inhibitors on mortality and stroke in patients with acute coronary syndrome or undergoing percutaneous coronary intervention

2013 ◽  
Vol 109 (01) ◽  
pp. 93-101 ◽  
Author(s):  
András Komócsi ◽  
András Vorobcsuk ◽  
Victor L. Serebruany ◽  
Dániel Aradi
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Meta Analysis ◽  
Coronary Intervention ◽  
Cardiovascular Death ◽  
P2y12 Receptor ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
Receptor Inhibition ◽  
Percutaneous Coronary ◽  
P2y12 Receptor Antagonist

SummaryAdministration of a P2Y12-receptor antagonist in addition to aspirin is mandatory in patients with acute coronary syndromes (ACS) or undergoing percutaneous coronary intervention (PCI) to reduce the occurrence of thrombotic events; however, their impact on mortality and stroke is unclear. We aimed to evaluate the influence of moderate (clopidogrel) or potent (prasugrel/ticagrelor) P2Y12-receptor inhibition on major cardiovascular outcomes among patients with ACS or undergoing PCI. Systematic literature search was performed to find randomised, controlled clinical trials comparing the clinical impact of clopidogrel with placebo or prasugrel/ticagrelor versus clopidogrel. Outcome measures included cardiovascular death, myocardial infarction (MI), total stroke and intracranial haemorrhage (ICH). Random-effects model with Mantel-Heanszel weighting was used to pool outcomes into a meta-analysis. Four studies comparing clopidogrel with placebo and five trials comparing clopidogrel with new P2Y12-receptor inhibitors were identified including a total of 107,473 patients. Compared to placebo, clopidogrel reduced the risk of cardiovascular death (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.87–0.99, p=0.02), MI (OR 0.80; 95%CI 0.74–0.88, p<0.00001) and stroke (OR 0.84; 95%CI 0.72–0.97, p=0.02), without influencing risk for ICH (OR 0.96;& 95%CI 0.69–1.33, p=0.79). Treatment with prasugrel/ticagrelor provided additional benefit over clopidogrel regarding cardiovascular mortality (OR 0.86; 95%CI 0.78–0.94, p=0.002) and MI (OR: 0.83; 95%CI 0.74–0.93, p<0.001), but no advantage in stroke (OR: 1.06; 95%CI 0.88–1.26, p=0.55) and in ICH (OR: 1.16; 95%CI 0.75–1.81; p=0.49) was observed. Increased potency of P2Y12-receptor inhibition is associated with decreased risk in cardiovascular death and MI; however, this association is not true in case of stroke, where potent P2Y12-receptor antagonists have no incremental benefit over clopidogrel.

scholarly journals Clopidogrel or ticagrelor alongside dabigatran in acute coronary syndrome and indication for NOAC: a study rationale

2021 ◽  
Author(s):  
Jasper Luijkx ◽  
Patty Winkler ◽  
Arnoud van 't Hof
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Acute Coronary Syndrome ◽  
Controlled Trial ◽  
Oral Anticoagulants ◽  
Academic Research ◽  
Coronary Intervention ◽  
Open Label ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
Percutaneous Coronary

The combination of oral anticoagulants with platelet inhibitors has been widely investigated in patients with coronary stenting and concomitant atrial fibrillation. In these patients, default therapy after percutaneous coronary intervention in acute coronary syndrome is clopidogrel plus non–vitamin K antagonist oral anticoagulant, omitting aspirin. However, in view of the high thromboembolic risk associated with acute coronary syndrome and the number of poor metabolizers for clopidogrel, investigation of alternative P2Y12-inhibitors is mandatory. This prospective, multicenter, open-label, registry-based, randomized, controlled trial aims to show the non-inferiority of dabigatran plus ticagrelor versus dabigatran plus clopidogrel in patients on chronic anticoagulants who undergo percutaneous coronary intervention in acute coronary syndrome. The primary end point is major bleeding as defined by the Bleeding Academic Research Consortium bleeding definition. Trial registration number: NL75644.096.21

scholarly journals Novel Oral Anticoagulants Following Percutaneous Coronary Intervention

2020 ◽  
Vol 13 (7) ◽  
Author(s):  
Bryan Q. Abadie ◽  
Christopher P. Cannon ◽  
Matthew A. Cavender
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Secondary Prevention ◽  
Coronary Revascularization ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Coronary Intervention ◽  
Novel Oral Anticoagulants ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
Percutaneous Coronary

Antiplatelet and anticoagulant medications are the cornerstone of therapy for patients with acute coronary syndrome and have also been shown to reduce recurrent cardiovascular events in patients with stable coronary disease. Whereas antiplatelet medications have been the preferred therapy for long-term secondary prevention, the development of novel oral anticoagulants has renewed interest in the use of anticoagulation to prevent atherosclerotic events. In patients with atrial fibrillation or other indications for anticoagulation, recent clinical trials have shown the benefit of double therapy with full-dose novel oral anticoagulants and P2Y12 inhibitors compared with regimens with vitamin K antagonists. In patients without an indication for anticoagulation, the use of low doses of the factor Xa inhibitor, rivaroxaban, has shown benefit. Clinicians have many pharmacological options when treating patients following percutaneous coronary intervention. This review discusses the evidence for the use of novel oral anticoagulants, with an emphasis on patient selection, choice of therapy, and appropriate dosing of anticoagulant and antiplatelet agents, in secondary prevention strategies for atherosclerosis following coronary revascularization for patients with and without a traditional indication for anticoagulation.

scholarly journals Platelet Inhibition in Acute Coronary Syndrome and Percutaneous Coronary Intervention: Insights from the Past and Present

2020 ◽  
Vol 120 (04) ◽  
pp. 565-578 ◽  
Author(s):  
Diana A. Gorog ◽  
Tobias Geisler
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Antiplatelet Therapy ◽  
Antiplatelet Agents ◽  
Bleeding Risk ◽  
Coronary Intervention ◽  
Platelet Function Test ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
The Past ◽  
Percutaneous Coronary

AbstractPlatelet activation and aggregation have a pivotal role in arterial thrombosis and in the pathogenesis of both acute coronary syndromes (ACS) and in the thrombotic complications that occur in patients undergoing percutaneous coronary intervention (PCI). The past 30 years has seen the progress from early trials of clopidogrel and glycoprotein IIb/IIIa inhibitors to the application of more potent P2Y12 inhibitors prasugrel and ticagrelor. Early enthusiasm for newer and more potent antiplatelet agents, which could reduce ischemic events, has led to the understanding of the importance of bleeding and a desire to individualize and optimize treatment. It has increasingly become apparent that the potency and duration of dual antiplatelet therapy (DAPT) has to reflect the balance between ischemic and bleeding risk. Recently, multiple strategies have been proposed to individualize DAPT intensity and duration to reduce the bleeding and ischemic risks. Strategies of de-escalation of DAPT intensity, as well as shorter (less than a year) or more prolonged (beyond a year) treatment have been proposed, as well as platelet function test and genotype guidance of P2Y12 inhibitor therapy. Herein, we provide an overview of the progress in the field of antiplatelet therapy for ACS and PCI over the years, showing the current directions of travel. Ongoing studies focusing on personalized antiplatelet treatment will hopefully yield further insight into ways of optimizing outcomes for the individual.

scholarly journals Clinical Outcomes after Percutaneous Coronary Intervention Over Time on the Basis of CYP2C19 Polymorphisms: Evidence from a Chinese Cohort

2021 ◽  
Author(s):  
Yang Zhang ◽  
Xiliang Zhao ◽  
Yicong Ye ◽  
Quan Li ◽  
Yong Zeng
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Primary Outcome ◽  
Coronary Intervention ◽  
Bleeding Complications ◽  
Loss Of Function ◽  
Coronary Syndrome ◽  
Percutaneous Coronary ◽  
Cyp2c19 Gene ◽  
Chinese Cohort

Abstract Purpose：To investigate the association between CYP2C19 gene polymorphism and the risk of ischemic and bleeding complications in the different period after percutaneous coronary intervention (PCI) among patients who received clopidogrel.Methods：Between October 2015 and January 2017, CYP2C19 genotyped patients who were treated clopidogrel after PCI were enrolled this observational cohort study. Included patients were categorized as non-loss-of-function metabolizers (NLOFMs), intermediate metabolizers (IMs) and poor metabolizers (PMs) based on CYP2C19 genotype. The primary outcome was a composite of any-cause mortality, nonfatal myocardial infarction, nonfatal ischemic stroke and stent thrombosis occurring during exposure to clopidogrel. The rates of clinical outcome events were compared between CYP2C19 phenotypes. Landmark analyses were processed at 90 days and 1-year post-PCI.Results：Of 1,341 patients, 161 (12.0%) had two copy of loss-of-function (LOF) alleles, 621(46.3%) had one LOF allele, and 559 (41.7%) had no LOF allele. At the 3-month follow-up, the primary outcome events were more frequent in carriers of two LOF alleles (5.6%) than in noncarriers (1.8%) (adjusted HR 2.944, 95% CI 1.184-7.321, p = 0.020). A similar finding was observed among in patients with acute coronary syndrome indications at the index PCI (adjusted HR 3.046, 95% CI 1.237-7.501, p = 0.015). These differences did not persist within the subsequent 9 months of follow-up, among either all-comers or subjects with ACS. The incidences of bleeding outcome events were similar among CYP2C19 phenotypes throughout the follow-up period.Conclusion：These data demonstrate a higher risk for ischemic events in patients with two CYP2C19 LOF alleles who are prescribed clopidogrel, previously seen at 3 months following PCI, that is not sustained for 12 months. These findings emphasize the need to place greater weight on a PM result during early antiplatelet therapy de-escalating decisions.

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