P2Y12-receptor-inhibiting antiplatelet strategies in acute coronary syndromes

2014 ◽  
Vol 34 (01) ◽  
pp. 20-28 ◽  
Author(s):  
K. Huber ◽  
T. Höchtl
Keyword(s):  
Acute Coronary Syndromes ◽  
Bleeding Risk ◽  
P2y12 Receptor ◽  
Antiplatelet Drugs ◽  
Major Adverse Cardiovascular Events ◽  
Onset Of Action ◽  
High Expectations ◽  
Coronary Syndromes ◽  
Underweight Patients ◽  
Special Patient

SummaryAntiplatelet therapy in acute coronary syndromes is essential for preventing stent thrombosis and for reducing major adverse cardiovascular events. Treatment strategy has changed over the last years by frequent use of more active agents inhibiting the ADP mediated activation of platelets instead of clopidogrel, such as prasugrel and ticagrelor. Compared to clopidogrel these modern antiplatelet drugs showed a significant reduction of efficacy endpoints as well as an acceptable safety profile in large multicenter randomized trials (TRITON TIMI 38, PLATO). Going in with higher efficacy a generally higher bleeding risk of prasugrel could be reduced by optimizing the maintenance dose in elderly and underweight patients (TRILOGY-ACS). However even prasugrel and ticagrelor have shown a delayed onset of action in special patient populations (e.g. STEMI) suggesting that the optimal ADP inhibitor has not been found yet. Results of the CHAMPION PHOENIX trial indicate that cangrelor, an intravenous agent, might fulfill these high expectations of an ideal platelet inhibitor in the first hours of an ACS in special patient cohorts.This review summarizes the results of most important clinical studies investigating the novel P2Y12 receptor inhibiting antiplatelet drugs.

scholarly journals Long-term outcomes in high-bleeding risk patients undergoing PCI for acute coronary syndromes: results from a large single-center pci registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Nicolas ◽  
D Cao ◽  
B Claessen ◽  
S Sartori ◽  
R Chandiramani ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Acute Coronary Syndromes ◽  
Bleeding Risk ◽  
Bleeding Complications ◽  
Major Adverse Cardiovascular Events ◽  
Bleeding Events ◽  
Increased Risk ◽  
Risk Patients ◽  
Coronary Syndromes ◽  
High Bleeding Risk

Abstract Introduction Current clinical guidelines recommend prolonged dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndromes (ACS). However, an extended DAPT duration in high-bleeding risk (HBR) patients amplifies the risk of post procedural complications. Hence, clinicians often face the dilemma of prolonging DAPT duration to prevent recurrent ischaemic events at the expense of increasing the incidence of bleeding in high-risk patients. The actual incidence of ischaemic and bleeding events in this particular population is not well elucidated. Purpose To evaluate one-year ischemic and bleeding outcomes following PCI for ACS in a real-world HBR population as defined by the Academic Research Consortium (ARC) consensus document. Methods We included all patients who presented with ACS to a high-volume single PCI centre from 2012 to 2017 and underwent PCI with 2nd generation drug-eluting stent implantation. Patients were classified as HBR if they met ≥1 major or ≥2 minor criteria according to the recent ARC-HBR consensus. The outcomes of interest were major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction (MI), and target lesion revascularization (TLR), and major bleeding events, including both peri-procedural and post-discharge bleeding. All outcomes were assessed at 1-year follow-up. The Kaplan-Meier method was used for time-to-event analyses. Results Out of 6,097 ACS patients included in this analysis, 2,717 (44.6%) fulfilled the ARC-HBR definition. Compared to non-HBR group, HBR patients were more frequently female, older, more likely to have cardiovascular risk factors (e.g., diabetes, hypertension, and hyperlipidemia) and complex coronary artery disease (e.g., multi-vessel disease, bifurcation lesions, and calcification). The 1-year incidence of MACE was significantly higher in HBR patients (16.3% vs. 8.1%, HR 2.16, 95% CI [1.81–2.59], p<0.001) (Figure 1A). This finding was driven by higher rates of all-cause death and MI (Figure 1B). The 1-year incidence of major bleeding was also significantly higher in HBR patients compared to non-HBR (11.1% vs. 3.1%, HR: 3.92, 95% CI 3.10–4.95; p<0.001). Conclusions HBR patients undergoing PCI for ACS are not only subject to bleeding complications but are also at an increased risk for ischemic events and all-cause mortality. Figure 1 Funding Acknowledgement Type of funding source: None

Antithrombotic therapy in the early phase of non-ST-elevation acute coronary syndromes: a systematic review and meta-analysis

2019 ◽  
Vol 6 (1) ◽  
pp. 43-56 ◽  
Author(s):  
Mattia Galli ◽  
Felicita Andreotti ◽  
Domenico D’Amario ◽  
Rocco Vergallo ◽  
Giovanni Maria Vescovo ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Antithrombotic Therapy ◽  
Acute Coronary Syndromes ◽  
Meta Analysis ◽  
Bleeding Risk ◽  
Major Adverse Cardiovascular Events ◽  
Clear Trend ◽  
Early Management ◽  
Coronary Syndromes ◽  
St Elevation

Abstract Aims Despite the increasing use of early invasive strategies in non-ST-elevation acute coronary syndromes (NSTE-ACS), optimal initial antithrombotic therapy (ATT) based on the safety/efficacy profile of all guideline-recommended combinations remains crucial for the early management of both medically and invasively treated NSTE-ACS patients. Methods and results Randomized controlled trials on ATT in NSTE-ACS/unstable angina reporting early (within 14 days) major adverse cardiovascular events (MACE) and major bleeding were selected. Overall, 3799 studies were screened, 117 clinical trials were assessed as potentially eligible, 20 trials were included in the study. According to treatment and type of intervention, nine different meta-analyses were performed including a total of 88 748 patients. A significant reduction of trial-defined MACE was found for aspirin vs. placebo [odds ratio (OR), 0.57; 95% confidence interval (CI), 0.34–0.96], heparin vs. placebo (OR, 0.38; 95% CI, 0.15–0.97), aspirin + heparin vs. placebo (OR, 0.32; 95% CI, 0.18–0.59), aspirin + heparin vs. aspirin (OR, 0.57; 95% CI, 0.42–0.79), aspirin + low molecular weight heparin (LMWH) vs. aspirin + unfractionated heparin (UFH; OR, 0.81; 95% CI, 0.69–0.95) and aspirin + ticagrelor/prasugrel + heparins vs. aspirin + clopidogrel + heparins (OR, 0.76; 95% CI, 0.62–0.94). A significant decrease in major bleeding was found only for fondaparinux vs. LMWH on the background of aspirin + clopidogrel (OR, 0.52; 95% CI, 0.44–0.62) despite a clear trend towards increased bleeding for heparin compared to aspirin, aspirin + heparin compared to placebo, aspirin + heparin compared to aspirin, aspirin + P2Y12inhibitors + UFH/LMWH compared to aspirin + UFH/LMWH, and aspirin + ticagrelor/prasugrel + heparins compared to aspirin + clopidogrel + heparins. Conclusion To our knowledge, these findings are the first to report the safety and efficacy of all the various combinations of currently recommended ATT for the early management of NSTE-ACS, providing a comprehensive evidence-base to guide decisions depending on the patients’ bleeding risk and treatment strategy.

scholarly journals Acute coronary syndromes with high thrombotic burden: therapeutic innovations

2020 ◽  
Vol 22 (Supplement_L) ◽  
pp. L97-L100
Author(s):  
Alberto Menozzi ◽  
Giorgio Caretta
Keyword(s):  
Acute Coronary Syndromes ◽  
Antiplatelet Agents ◽  
Bleeding Risk ◽  
Platelet Inhibition ◽  
Onset Of Action ◽  
Thrombotic Risk ◽  
P2y12 Inhibitors ◽  
Oral Medications ◽  
Platelet Receptor ◽  
Coronary Syndromes

Abstract Antiplatelet agents represent one of the cornerstones of drug therapy for acute coronary syndromes (ACS). In the last decade, the arrival of prasugrel and ticagrelor, faster and more powerful oral platelet receptor P2Y12 inhibitors compared to clopidogrel, significantly improved platelet inhibition in patients with ACS. However, the reduction of thrombotic risk came at the cost of increased bleeding risk. Despite having similar indications, prasugrel and ticagrelor have different characteristics and methods of use, essentially due to a different design of the trials in which they have been studied. The optimal use of these antiplatelets in clinical practice should therefore be tailored in individual patients. In the acute phase of ACS with high thrombotic burden, all oral P2Y12 inhibitors have limitations, mainly due to the delay of onset of action related to oral administration. In this scenario, parenteral antiplatelet agents (glycoprotein inhibitors IIb/IIIa and cangrelor) may play a key role in case of percutaneous coronary interventions of high thrombotic coronary lesions and in the prevention of early thrombotic complications. Cangrelor, an intravenous inhibitor of the P2Y2 receptor, has peculiar pharmacokinetic and pharmacodynamic characteristics that make it particularly suitable to be used as an antiplatelet during coronary angioplasty as it achieves a rapid and powerful antiplatelet effect in patients not pretreated with oral medications, and has a favourable safety profile in relation to the bleeding risk.

Antiplatelet Therapy in Acute Coronary Syndromes

2010 ◽  
Vol 6 (1) ◽  
pp. 58
Author(s):  
Sasha Koul ◽  
David Erlinge ◽  
◽  
Keyword(s):  
Platelet Function ◽  
Acute Coronary Syndromes ◽  
New Drugs ◽  
Antiplatelet Drugs ◽  
Bleeding Complications ◽  
Great Promise ◽  
Mortality Data ◽  
Poor Responders ◽  
Coronary Syndromes

Drugs inhibiting platelet function play a major role in the treatment of acute coronary syndromes (ACS). The first drug used, which is still considered the cornerstone of therapy today, is aspirin. Although very impressive in acutely decreasing rates of myocardial infarction as well as death, long-term data are scarce, despite our current recommendation for lifelong aspirin. The thienopyridines, most notably clopidogrel, are the next line of antiplatelet drugs. Well-documented data support the usage of clopidogrel for non-STEMI-ACS (NSTE-ACS). Although positive mortality data exist regarding clopidogrel and STEMI patients in a medically treated population, including thrombolysis, no larger amounts of randomised data exist in a primary PCI setting. Poor responders to aspirin and/or clopidogrel are a clinical problem, with these individuals constituting a higherrisk group for recurrent ischaemic events. Whereas very little can be done regarding aspirin resistance, clopidogrel resistance might be diminished by increasing the dosage or changing to more potent and newer-generation antiplatelet drugs. The role of glycoprotein IIb/IIIa inhibitors has diminished drastically and instead paved the way for thrombin antagonists (bivalirudin), which have fewer bleeding complications with resulting better long-term mortality. Novel adenosine diphosphate (ADP)-receptor blockers such as prasugrel and ticagrelor have shown increased efficacy over clopidogrel and hold great promise for the future. However, not all patients may benefit from these new drugs and economic constraints may also limit their use. Platelet function tests could possibly help in identifying risk groups in need of stronger platelet inhibition.

Is there Sex-related Outcome Difference According to oral P2Y12 Inhibitors in Patients with Acute Coronary Syndromes? A Systematic Review and Meta-Analysis of 107,126 Patients

2019 ◽  
Vol 17 (2) ◽  
pp. 191-203
Author(s):  
Oliver Brown ◽  
Jennifer Rossington ◽  
Gill Louise Buchanan ◽  
Giuseppe Patti ◽  
Angela Hoye
Keyword(s):  
Systematic Review ◽  
Acute Coronary Syndromes ◽  
Meta Analysis ◽  
Indirect Comparison ◽  
Bleeding Risk ◽  
Cardiovascular Death ◽  
P2y12 Inhibitors ◽  
Significant Difference ◽  
Coronary Syndromes ◽  
Randomised Controlled

Background and Objectives: The majority of patients included in trials of anti-platelet therapy are male. This systematic review and meta-analysis aimed to determine whether, in addition to aspirin, P2Y12 blockade is beneficial in both women and men with acute coronary syndromes. </P><P> Methods: Electronic databases were searched and nine eligible randomised controlled studies were identified that had sex-specific clinical outcomes (n=107,126 patients). Risk Ratios (RR) and 95% Confidence Intervals (CI) were calculated for a composite of cardiovascular death, myocardial infarction or stroke (MACE), and a safety endpoint of major bleeding for each sex. Indirect comparison analysis was performed to statistically compare ticagrelor against prasugrel. </P><P> Results: Compared to aspirin alone, clopidogrel reduced MACE in men (RR, 0.79; 95% CI, 0.68 to 0.92; p=0.003), but was not statistically significant in women (RR, 0.88; 95% CI, 0.75 to 1.02, p=0.08). Clopidogrel therapy significantly increased bleeding in women but not men. Compared to clopidogrel, prasugrel was beneficial in men (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02) but not statistically significant in women (RR, 0.94; 95% CI, 0.83 to 1.06; p=0.30); ticagrelor reduced MACE in both men (RR, 0.85; 95% CI, 0.77 to 0.94; p=0.001) and women (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02). Indirect comparison demonstrated no significant difference between ticagrelor and prasugrel in either sex. Compared to clopidogrel, ticagrelor and prasugrel increased bleeding risk in both women and men. </P><P> Conclusion: In summary, in comparison to monotherapy with aspirin, P2Y12 inhibitors reduce MACE in women and men. Ticagrelor was shown to be superior to clopidogrel in both sexes. Prasugrel showed a statistically significant benefit only in men; however indirect comparison did not demonstrate superiority of ticagrelor over prasugrel in women.

scholarly journals Bleeding risk assessment and comorbidities in elderly patients with acute coronary syndromes

2016 ◽  
Vol 35 (4) ◽  
pp. 247-248
Author(s):  
Albert Ariza-Solé ◽  
Francesc Formiga ◽  
Eva Bernal ◽  
Alberto Garay
Keyword(s):  
Risk Assessment ◽  
Elderly Patients ◽  
Acute Coronary Syndromes ◽  
Bleeding Risk ◽  
Coronary Syndromes

Overview of pleiotropic effects of platelet P2Y12 receptor inhibitors

2014 ◽  
Vol 112 (08) ◽  
pp. 224-242 ◽  
Author(s):  
Marek Koziński ◽  
Małgorzata Ostrowska ◽  
Tomasz Fabiszak ◽  
Eliano Navarese ◽  
Przemysław Paciorek ◽  
...  
Keyword(s):  
Acute Coronary Syndromes ◽  
Dual Antiplatelet Therapy ◽  
Mechanisms Of Action ◽  
Pleiotropic Effects ◽  
P2y12 Receptor ◽  
Occurrence Rate ◽  
Percutaneous Coronary Interventions ◽  
Percutaneous Coronary ◽  
Coronary Syndromes ◽  
Receptor Blockers

SummaryDual antiplatelet therapy consisting of one of the P2Y12 receptor inhibitors in conjunction with aspirin is the mainstay of treatment for patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary interventions (PCI). In recent years, multiple extra-platelet features of P2Y12 receptor antagonists have been reported in numerous clinical trials. The aim of this review is to summarise reported pleiotropic effects of clopidogrel, prasugrel, ticagrelor and other P2Y12 receptor blockers. We included observations made both in human and in animal models, together with proposed mechanisms of action for described features. If confirmed in randomised studies and properly applied to everyday practice, the observed extra-platelet actions could enable us to improve efficacy of ACS and post-PCI treatment, as well as to confine mortality and occurrence rate of cardiovascular events.

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