Effects of Ticagrelor, Prasugrel, or Clopidogrel on Endothelial Function and Other Vascular Biomarkers

Gianni, Umberto; Frigoli, Enrico; Monti, Monia; Ciociano, Nestor; Karagiannis, Alexios; Heg, Dik; Leonardi, Sergio; Rizzotti, Diego; Mirizzi, A Mandurino; Royen, Niels van; Leeuwen, Maarten van; Janssens, Gladys N.; Räber, Lorenz; Ariotti, Sara; Valgimigli, Marco; Windecker, Stephan; Rimoldi, Stefano F.; Rexhaj, Emrush; Brugaletta, Salvatore; Sabaté, Manel; Ortega‐Paz, Luis; Akkerhuis, K. Martijn; Berge, J

doi:10.1016/j.jcin.2018.04.022

Cited by 48 publications

(53 citation statements)

References 19 publications

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“…Ticagrelor treatment for 30 days improved endothelial function compared to clopidogrel in patients with a previous ACS and this was correlated to a significant increase in plasma adenosine levels 199 . In contrast, four weeks of treatment with ticagrelor in patients with a previous ACS was not associated with improvement in endothelial function compared to treatment with clopidogrel or prasugrel 200 . Additionally, plasma adenosine levels were unaffected.…”

Section: Effect Of Ticagrelor Treatment On the Endotheliummentioning

confidence: 56%

Remote ischemic conditioning protects against endothelial ischemia-reperfusion injury via a glucagon-like peptide-1 receptor-mediated mechanism in humans

Verouhis¹,

Saleh²,

Settergren³

et al. 2019

International Journal of Cardiology

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Section: Effect Of Ticagrelor Treatment On the Endotheliummentioning

confidence: 56%

Remote ischemic conditioning protects against endothelial ischemia-reperfusion injury via a glucagon-like peptide-1 receptor-mediated mechanism in humans

Verouhis¹,

Saleh²,

Settergren³

et al. 2019

International Journal of Cardiology

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“…It is possible that these vascular properties of ticagrelor may result in an increased bleeding tendency in the presence of simultaneous inhibition of platelet P2Y 12 . The importance of these effects is uncertain, however, as more recent reports in humans suggest no difference in the vascular effects of thienopyridines and ticagrelor …”

Section: Discussionmentioning

confidence: 99%

DT‐678 inhibits platelet activation with lower tendency for bleeding compared to existing P2Y₁₂ antagonists

Lauver

Kuszynski

Christian

et al. 2019

Pharmacology Res & Perspec

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The novel clopidogrel conjugate, DT‐678, is an effective inhibitor of platelets and thrombosis in preclinical studies. However, a comparison of the bleeding risk with DT‐678 and currently approved P2Y 12 antagonists has yet to be determined. The objective of this study was to evaluate the bleeding tendency of animals treated with clopidogrel, ticagrelor, and DT‐678. Ninety‐one New Zealand white rabbits were randomized to one of 13 treatment groups (n = 7). Platelet activation was assessed by flow cytometry and light transmission aggregometry before and after the administration of various doses of DT‐678, clopidogrel, and ticagrelor. Tongue template bleeding times were also measured before and after drug treatment. Treatment with P2Y 12 receptor antagonists caused a dose‐dependent reduction in markers of platelet activation (P‐selectin and integrin α IIb β 3 ) and aggregation in response to adenosine diphosphate stimulation. At the same doses required for platelet inhibition, clopidogrel and ticagrelor significantly prolonged bleeding times, while DT‐678 did not. DT‐678 and the FDA‐approved P2Y 12 antagonists clopidogrel and ticagrelor are effective inhibitors of platelet activation and aggregation. However, unlike clopidogrel and ticagrelor, DT‐678 did not prolong bleeding times at equally effective antiplatelet doses. The results suggest a more favorable benefit/risk ratio for DT‐678 and potential utility as part of a dual antiplatelet therapy regimen.

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“…Ticagrelor had anti-inflammatory effects including reduced formation of platelet-neutrophil aggregates in inflammation models and more profound reduction in Il-6 in a human sepsis model as compared to clopidogrel, suggesting that stronger inhibition of the P2Y12 receptor (ticagrelor) may provide greater anti-inflammatory effect (Nylander and Schulz 2016). Off-target effects of ticagrelor on endothelial function and vascular biomarkers have been speculated on, but a recent study comparing ticagrelor to prasugrel and clopidogrel found no evidence for any non-platelet-mediated effects in post-acute coronary syndrome patients (Ariotti et al 2018).…”

Section: Secondary Prevention Of Atherothrombosis In Patients With Armentioning

confidence: 99%

Antithrombotic Therapy: Prevention and Treatment of Atherosclerosis and Atherothrombosis

Olie

Meijden

Spronk

et al. 2020

Handbook of Experimental Pharmacology

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Atherosclerosis is a multifactorial vascular disease that develops in the course of a lifetime. Numerous risk factors for atherosclerosis have been identified, mostly inflicting pro-inflammatory effects. Vessel injury, such as occurring during erosion or rupture of atherosclerotic lesions triggers blood coagulation, in attempt to maintain hemostasis (protect against bleeding). However, thrombo-inflammatory mechanisms may drive blood coagulation such that thrombosis develops, the key process underlying myocardial infarction and ischemic stroke (not due to embolization from the heart). In the blood coagulation system, platelets and coagulation proteins are both essential elements. Hyperreactivity of blood coagulation aggravates atherosclerosis in preclinical models. Pharmacologic inhibition of blood coagulation, either with platelet inhibitors, or better documented with anticoagulants, or both, limits the risk of thrombosis and may potentially reverse atherosclerosis burden, although the latter evidence is still based on animal experimentation. Patients at risk of atherothrombotic complications should receive a single antiplatelet agent (acetylsalicylic acid, ASA, or clopidogrel); those who survived an atherothrombotic event will be prescribed temporary dual antiplatelet therapy (ASA plus a P2Y12 inhibitor) in case of myocardial infarction (6-12 months), or stroke (<6 weeks), followed by a single antiplatelet agent indefinitely. High risk for thrombosis patients (such as those with peripheral artery disease) benefit from a combination of an anticoagulant and ASA. The price of gained efficacy is always increased risk of (major) bleeding; while tailoring therapy to individual needs may limit the risks to some extent, new generations of agents that target less critical elements of hemostasis and coagulation mechanisms are needed to maintain efficacy while reducing bleeding risks.

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Effects of Ticagrelor, Prasugrel, or Clopidogrel on Endothelial Function and Other Vascular Biomarkers

Cited by 48 publications

References 19 publications

Remote ischemic conditioning protects against endothelial ischemia-reperfusion injury via a glucagon-like peptide-1 receptor-mediated mechanism in humans

Remote ischemic conditioning protects against endothelial ischemia-reperfusion injury via a glucagon-like peptide-1 receptor-mediated mechanism in humans

DT‐678 inhibits platelet activation with lower tendency for bleeding compared to existing P2Y₁₂ antagonists

Antithrombotic Therapy: Prevention and Treatment of Atherosclerosis and Atherothrombosis

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Effects of Ticagrelor, Prasugrel, or Clopidogrel on Endothelial Function and Other Vascular Biomarkers

Cited by 48 publications

References 19 publications

Remote ischemic conditioning protects against endothelial ischemia-reperfusion injury via a glucagon-like peptide-1 receptor-mediated mechanism in humans

Remote ischemic conditioning protects against endothelial ischemia-reperfusion injury via a glucagon-like peptide-1 receptor-mediated mechanism in humans

DT‐678 inhibits platelet activation with lower tendency for bleeding compared to existing P2Y12 antagonists

Antithrombotic Therapy: Prevention and Treatment of Atherosclerosis and Atherothrombosis

Contact Info

Product

Resources

About

DT‐678 inhibits platelet activation with lower tendency for bleeding compared to existing P2Y₁₂ antagonists