SAR216471, an alternative to the use of currently available P2Y12 receptor inhibitors?

Delesque-Touchard, Nathalie; Pflieger, A M; Bonnet-Lignon, Sandrine; Millet, L; Salel, Véronique; Boldron, Christophe; Lassalle, Gilbert; Herbert, Jean‐Marc; Savi, Pierre; Bono, Françoise

doi:10.1016/j.thromres.2014.06.034

Cited by 18 publications

(33 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further studies are warranted to evaluate the clinical efficacy and safety of such a novel approach in acute settings where rapid platelet inhibition is desirable, as for example in ACS patients [ 168 , 169 ]. Two other novel highly potent inhibitors of P2Y 12 are under development, AZD1283 and SAR216471 [ 170 , 171 ], the latter being in the most advanced stage of development. It was associated with less bleeding, higher selectivity, and equivalent antithrombotic efficacy compared to ticagrelor in a rat model and is currently undergoing a phase II study (NCT03384966).…”

Section: Antiplatelet Agents Under Preclinical/clinical Developmentmentioning

confidence: 99%

Current and Novel Antiplatelet Therapies for the Treatment of Cardiovascular Diseases

Jourdi

Lordkipanidzé

Philippe

et al. 2021

IJMS

View full text Add to dashboard Cite

Over the last decades, antiplatelet agents, mainly aspirin and P2Y12 receptor antagonists, have significantly reduced morbidity and mortality associated with arterial thrombosis. Their pharmacological characteristics, including pharmacokinetic/pharmacodynamics profiles, have been extensively studied, and a significant number of clinical trials assessing their efficacy and safety in various clinical settings have established antithrombotic efficacy. Notwithstanding, antiplatelet agents carry an inherent risk of bleeding. Given that bleeding is associated with adverse cardiovascular outcomes and mortality, there is an unmet clinical need to develop novel antiplatelet therapies that inhibit thrombosis while maintaining hemostasis. In this review, we present the currently available antiplatelet agents, with a particular focus on their targets, pharmacological characteristics, and patterns of use. We will further discuss the novel antiplatelet therapies in the pipeline, with the goal of improved clinical outcomes among patients with atherothrombotic diseases.

show abstract

Section: Antiplatelet Agents Under Preclinical/clinical Developmentmentioning

confidence: 99%

Current and Novel Antiplatelet Therapies for the Treatment of Cardiovascular Diseases

Jourdi

Lordkipanidzé

Philippe

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…100 Also, SAR216471 and AZD1283 are reversible, nonthienopyridine inhibitors of P2Y 12 , which provided good antithrombotic efficacy with a superior safety profile compared to the current P2Y 12 inhibitors in preclinical models (Table 1 and Figure 1). 101,102 Platelet 12-Lipoxygenase 12-Lipoxygenase (12-LOX) uses arachidonic acid to form bioactive metabolites that have been linked with regulation of PAR-4-and GPVI-mediated signaling pathways and FcgRIIa-mediated thrombosis. 103,104 ML355 is the first 12-LOX inhibitor and demonstrated dose-dependent inhibition of human platelet aggregation in vitro (Table 1 and Figure 1).…”

Section: Adenosine Diphosphate Receptorsmentioning

confidence: 99%

Novel Antiplatelet Agents in Cardiovascular Disease

Tscharre

Michelson

Gremmel

2020

J Cardiovasc Pharmacol Ther

View full text Add to dashboard Cite

Antiplatelet therapy reduces atherothrombotic risk and has therefore become a cornerstone in the treatment of cardiovascular disease. Aspirin, adenosine diphosphate P2Y12 receptor antagonists, glycoprotein IIb/IIIa inhibitors, and the thrombin receptor blocker vorapaxar are effective antiplatelet agents but significantly increase the risk of bleeding. Moreover, atherothrombotic events still impair the prognosis of many patients with cardiovascular disease despite established antiplatelet therapy. Over the last years, advances in the understanding of thrombus formation and hemostasis led to the discovery of various new receptors and signaling pathways of platelet activation. As a consequence, many new antiplatelet agents with high antithrombotic efficacy and supposedly only moderate effects on regular hemostasis have been developed and yielded promising results in preclinical and early clinical studies. Although their long journey from animal studies to randomized clinical trials and finally administration in daily clinical routine has just begun, some of the new agents may in the future become meaningful additions to the pharmacological armamentarium in cardiovascular disease.

show abstract

“…Novel Therapeutic Targets Novel P2Y 12 and P2Y 1 Inhibitors Novel P2Y 12 inhibitors include selatogrel, AZD1283, and SAR216471 (►Table 2). 92,93 Recently, in a phase II study, selatogrel was shown to provide rapid onset of potent, consistent platelet inhibition when given by subcutaneous injection. 93 In animal models, the platelet P2Y 1 inhibitor BMS-884775 demonstrated similar efficacy to clopidogrel with less bleeding.…”

Section: Less Intensive or Shorter Antiplatelet Therapymentioning

confidence: 99%

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

Gorog

Geisler

2020

Thromb Haemost

View full text Add to dashboard Cite

Platelet 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.

show abstract

SAR216471, an alternative to the use of currently available P2Y12 receptor inhibitors?

Cited by 18 publications

References 27 publications

Current and Novel Antiplatelet Therapies for the Treatment of Cardiovascular Diseases

Current and Novel Antiplatelet Therapies for the Treatment of Cardiovascular Diseases

Novel Antiplatelet Agents in Cardiovascular Disease

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

Contact Info

Product

Resources

About