Pharmacologic Therapy for Non ST-segment Elevation Acute Coronary Syndromes: Focus on Antithrombotic Therapy

Danchin, Nicolás; Aïssaoui, Nadia

doi:10.1007/s10557-010-6259-3

Cited by 3 publications

(1 citation statement)

References 39 publications

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“…By blocking the final pathway of platelet aggregation, in which platelets bridge with fibrinogen, glycoprotein IIb/IIIa inhibitors can disaggregate platelets and thereby potentially reduce thrombotic complications as well as increase bleeding risk in patients undergoing PCI (Danchin and Aïssaoui, ). Indeed, bleeding complications are common features of GPIs.…”

Section: Discussionmentioning

confidence: 99%

Antithrombotic effect of Z4A5 on coronary thrombosis in a canine model of acute unstable angina

Jing¹,

Li²,

Zhang³

et al. 2013

British J Pharmacology

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BACKGROUND AND PURPOSEThe glycoprotein IIb/IIIa receptor is the final common pathway of platelet aggregation, regardless of the agonist, and thus represents an ideal therapeutic target for blocking coronary thrombosis. In this study, the anti-platelet and antithrombotic actions of Z4A5, a new glycoprotein IIb/IIIa receptor inhibitor, were evaluated in a canine model of acute unstable angina. EXPERIMENTAL APPROACHZ4A5 was given i.v. as a bolus followed by 60 min of continuous infusion at doses of 30 mg·kg -1 + 1 mg·kg. Its antithrombotic effect was evaluated in a model of coronary thrombosis, the injured, stenosed left circumflex coronary artery, in which platelet-dependent cyclic flow reductions (CFRs) were induced by vascular compression and constriction to simulate clinical acute unstable angina. Platelet aggregation and coagulation parameters were determined in platelet-rich plasma and platelet poor plasma respectively. KEY RESULTSThe Z4A5 infusion induced a dose-dependent reduction in CFR frequency, which returned to baseline levels after the termination of the infusion at low doses. At medium dose that inhibited most part of platelet aggregation, it increased tongue bleeding time marginally with no dramatic changes in haemodynamic and coagulation parameters. Furthermore, the inhibition of ADP-induced platelet aggregation and prolonged bleeding time observed during Z4A5 infusion reverted to baseline levels after the termination of the infusion. CONCLUSIONS AND IMPLICATIONSZ4A5 is an effective antithrombotic agent for coronary artery thrombosis with a rapid-on and rapid-off pharmacological profile, and could be used as an alternative treatment of coronary artery ischaemic syndromes.

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Section: Discussionmentioning

confidence: 99%

Antithrombotic effect of Z4A5 on coronary thrombosis in a canine model of acute unstable angina

Jing¹,

Li²,

Zhang³

et al. 2013

British J Pharmacology

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Clopidogrel pre-treatment is associated with reduced in-hospital mortality in primary percutaneous coronary intervention for acute ST-elevation myocardial infarction

Dörler

Edlinger

Altenberger

et al. 2011

European Heart Journal

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AIMS Pre-treatment with clopidogrel results in a reduction of ischaemic events in non-ST-elevation acute coronary syndromes. Data on upstream clopidogrel in the setting of primary percutaneous coronary intervention (PCI) are limited. The aim of this study was to investigate whether clopidogrel loading before arrival at the PCI centre may result in an improved outcome of primary PCI for ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS In a multicentre registry of acute PCI, 5955 patients undergoing primary PCI in Austria between January 2005 and December 2009 were prospectively enrolled. The patients consisted of two groups, a clopidogrel pre-treatment group (n = 1635 patients) receiving clopidogrel before arrival at the PCI centre and a peri-interventional clopidogrel group (n = 4320 patients) receiving clopidogrel at a later stage. Multiple logistic regression analysis including major confounding factors stratified by the participating centres was applied to investigate the effect of pre-treatment with clopidogrel on the in-hospital mortality. Additionally, two subgroups, with or without the use of GP IIb/IIIa antagonist therapy in the catheterization laboratory, were analysed. On univariate analysis, clopidogrel pre-treatment was associated with a reduced in-hospital mortality (3.4 vs. 6.1%, P< 0.01) after primary PCI. On multivariate analysis, clopidogrel pre-treatment remained an independent predictor of in-hospital mortality [odds ratio (OR) = 0.60, 95% confidence interval (CI) 0.35-0.99; P =0.048], especially in patients receiving additional GP IIb/IIIa antagonist therapy in the catheterization laboratory (OR = 0.40, 95% CI 0.19-0.83; P =0.01). CONCLUSION Clopidogrel pre-treatment before arrival at the PCI centre is associated with reduced mortality in a real world setting of primary PCI. These results strongly support the recommendation of clopidogrel treatment 'as soon as possible' in patients with STEMI undergoing pimary PCI.

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Ticagrelor: a P2Y₁₂antagonist for use in acute coronary syndromes

Wijeyeratne

Joshi

Heptinstall

2012

Expert Review of Clinical Pharmacology

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Agents that inhibit platelet function are used routinely in the treatment and prevention of acute coronary syndromes. The main antiplatelet treatments used combine aspirin with one of the thienopyridine P2Y(12) antagonists, either clopidogrel or prasugrel. By blocking the synthesis of thromboxane A(2) in platelets and by blocking the effects of ADP, respectively, these agents reduce platelet activity, platelet aggregation and thrombus formation. Ticagrelor (marketed by AstraZeneca as Brilinta™ in the USA, and as Brilique(®) or Possia(®) in Europe) is a cyclopentyl-triazolo-pyrimidine, a new chemical class of P2Y(12) antagonist that is now approved for use in the wide spectrum of acute coronary syndromes. In this article we provide an overview of ticagrelor. We discuss the differences in mode of action compared with other P2Y(12) antagonists, examine its pharmacodynamic, pharmacokinetic and safety profile, and summarize the various clinical trials that have provided information on its efficacy in combination with aspirin. Ticagrelor appears to overcome some of the difficulties that have been encountered with other antiplatelet treatments, clopidogrel in particular.

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Pharmacologic Therapy for Non ST-segment Elevation Acute Coronary Syndromes: Focus on Antithrombotic Therapy

Cited by 3 publications

References 39 publications

Antithrombotic effect of Z4A5 on coronary thrombosis in a canine model of acute unstable angina

Antithrombotic effect of Z4A5 on coronary thrombosis in a canine model of acute unstable angina

Clopidogrel pre-treatment is associated with reduced in-hospital mortality in primary percutaneous coronary intervention for acute ST-elevation myocardial infarction

Ticagrelor: a P2Y₁₂antagonist for use in acute coronary syndromes

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Pharmacologic Therapy for Non ST-segment Elevation Acute Coronary Syndromes: Focus on Antithrombotic Therapy

Cited by 3 publications

References 39 publications

Antithrombotic effect of Z4A5 on coronary thrombosis in a canine model of acute unstable angina

Antithrombotic effect of Z4A5 on coronary thrombosis in a canine model of acute unstable angina

Clopidogrel pre-treatment is associated with reduced in-hospital mortality in primary percutaneous coronary intervention for acute ST-elevation myocardial infarction

Ticagrelor: a P2Y12antagonist for use in acute coronary syndromes

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Product

Resources

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Ticagrelor: a P2Y₁₂antagonist for use in acute coronary syndromes