Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction

Peter Sinnaeve; Gregor Fahrni; Dan Schelfaut; Alessandro Spirito; Christian Mueller; Jean Marie Frenoux; Abdel Hmissi; Corine Bernaud; Mike Ufer; Tiziano Moccetti; Shaul Atar; Marco Valgimigli

doi:10.1016/j.jacc.2020.03.059

Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction

Peter Sinnaeve
, Gregor Fahrni
, Dan Schelfaut
, Alessandro Spirito
, Christian Mueller
, Jean Marie Frenoux
, Abdel Hmissi
, Corine Bernaud
, Mike Ufer
, Tiziano Moccetti
, Shaul Atar
, Marco Valgimigli

Bar-Ilan University - Azrieli Faculty of Medicine

Research output: Contribution to journal › Article › peer-review

66 Scopus citations

Abstract

Background: Oral P2Y₁₂ receptor antagonists exhibit delayed onset of platelet inhibition in patients with acute myocardial infarction (AMI). Selatogrel is a potent, highly selective, and reversible P2Y₁₂ receptor antagonist with a rapid onset and short duration of action. Objectives: This study sought to assess inhibition of platelet aggregation following subcutaneous administration of selatogrel in patients with AMI. Methods: Patients with AMI were randomized to a single subcutaneous dose of selatogrel of 8 or 16 mg. The primary endpoint was response to treatment (P2Y₁₂ reaction units <100; measured by VerifyNow) at 30 min post-dose. Safety was assessed up to 48 h post-injection. Results: Forty-seven patients received selatogrel 8 mg (n = 24) or 16 mg (n = 23) followed by ticagrelor (n = 43) or clopidogrel (n = 1). The proportion of responders 30 min post-dose was 91% (one-sided 97.5% confidence interval [CI]: 80% to 100%) and 96% (97.5% CI: 87% to 100%) with 8 and 16 mg, respectively (p values for responders >85% target; p = 0.142 and p = 0.009, respectively). Response rates were independent from type of AMI presentation, age, or sex. A similar response rate was observed at 15 min (8 mg: 75% [97.5% CI: 58% to 100%]; 16 mg: 91% [97.5% CI: 80% to 100%]), which was sustained at 60 min post-dose (8 mg: 75% [97.5% CI: 58% to 100%]; 16 mg: 96% [97.5% CI: 87% to 100%]). At 15 min, median P2Y₁₂ reaction units was 51 (range: 4 to 208) for 8 mg and 9 (range: 2 to 175) for 16 mg. Selatogrel was well tolerated, without major bleeding complications. Conclusions: Single-dose subcutaneous administration of selatogrel in patients with AMI was safe and induced a profound, rapid, and dose-related antiplatelet response.

Original language	English
Pages (from-to)	2588-2597
Number of pages	10
Journal	Journal of the American College of Cardiology
Volume	75
Issue number	20
DOIs	https://doi.org/10.1016/j.jacc.2020.03.059
State	Published - 26 May 2020

Bibliographical note

Publisher Copyright:
© 2020

Funding

The authors thank all patients, study investigators, study staff, and nursing teams for their participation in this research. The authors acknowledge Yosef Mansour, PhD, an employee of Idorsia Pharmaceuticals Ltd. for providing medical writing support during manuscript development. The authors also acknowledge the contribution of Claes Held and Robert Wilcox and their roles in the independent safety event committee. This study was sponsored by Idorsia Pharmaceuticals Ltd. Dr. Sinnaeve has received consultancy and/or speaker fees and grants from AstraZeneca and Daiichi-Sankyo all of which were collected institutionally; and is a clinical investigator for the Fonds voor Wetenschappelijk Onderzoek—Vlaanderen. Dr. Mueller has received grants and personal fees from Idorsia Pharmaceuticals Ltd. Dr. Frenoux, Mr. Hmissi, Dr. Bernaud, and Dr. Ufer are employees and shareholders of Idorsia Pharmaceuticals Ltd. Dr. Valgimigli has received grants and/or personal fees from AstraZeneca, Terumo, Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Opsens, Bayer, CoreFLOW, Idorsia Pharmaceuticals Ltd., Universität Basel Department Klinische Forschung, Vifor, Bristol-Myers Squibb SA, iVascular, and Medscape. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. This study was sponsored by Idorsia Pharmaceuticals Ltd. Dr. Sinnaeve has received consultancy and/or speaker fees and grants from AstraZeneca and Daiichi-Sankyo all of which were collected institutionally; and is a clinical investigator for the Fonds voor Wetenschappelijk Onderzoek—Vlaanderen. Dr. Mueller has received grants and personal fees from Idorsia Pharmaceuticals Ltd. Dr. Frenoux, Mr. Hmissi, Dr. Bernaud, and Dr. Ufer are employees and shareholders of Idorsia Pharmaceuticals Ltd. Dr. Valgimigli has received grants and/or personal fees from AstraZeneca, Terumo, Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Opsens, Bayer, CoreFLOW, Idorsia Pharmaceuticals Ltd., Universität Basel Department Klinische Forschung, Vifor, Bristol-Myers Squibb SA, iVascular, and Medscape. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Funders
Fonds voor Wetenschappelijk Onderzoek—Vlaanderen
Universität Basel Department Klinische Forschung
Vifor
Bristol-Myers Squibb
AstraZeneca
Idorsia Pharmaceuticals

Keywords

P2Y
ST-segment elevation myocardial infarction
acute coronary syndrome
acute myocardial infarction
non–ST-segment elevation myocardial infarction
subcutaneous

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10.1016/j.jacc.2020.03.059

Cite this

Sinnaeve, P., Fahrni, G., Schelfaut, D., Spirito, A., Mueller, C., Frenoux, J. M., Hmissi, A., Bernaud, C., Ufer, M., Moccetti, T., Atar, S., & Valgimigli, M. (2020). Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction. Journal of the American College of Cardiology, 75(20), 2588-2597. https://doi.org/10.1016/j.jacc.2020.03.059

@article{21a5acad1c44467f820ac624332ccbb5,

title = "Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction",

abstract = "Background: Oral P2Y12 receptor antagonists exhibit delayed onset of platelet inhibition in patients with acute myocardial infarction (AMI). Selatogrel is a potent, highly selective, and reversible P2Y12 receptor antagonist with a rapid onset and short duration of action. Objectives: This study sought to assess inhibition of platelet aggregation following subcutaneous administration of selatogrel in patients with AMI. Methods: Patients with AMI were randomized to a single subcutaneous dose of selatogrel of 8 or 16 mg. The primary endpoint was response to treatment (P2Y12 reaction units <100; measured by VerifyNow) at 30 min post-dose. Safety was assessed up to 48 h post-injection. Results: Forty-seven patients received selatogrel 8 mg (n = 24) or 16 mg (n = 23) followed by ticagrelor (n = 43) or clopidogrel (n = 1). The proportion of responders 30 min post-dose was 91\% (one-sided 97.5\% confidence interval [CI]: 80\% to 100\%) and 96\% (97.5\% CI: 87\% to 100\%) with 8 and 16 mg, respectively (p values for responders >85\% target; p = 0.142 and p = 0.009, respectively). Response rates were independent from type of AMI presentation, age, or sex. A similar response rate was observed at 15 min (8 mg: 75\% [97.5\% CI: 58\% to 100\%]; 16 mg: 91\% [97.5\% CI: 80\% to 100\%]), which was sustained at 60 min post-dose (8 mg: 75\% [97.5\% CI: 58\% to 100\%]; 16 mg: 96\% [97.5\% CI: 87\% to 100\%]). At 15 min, median P2Y12 reaction units was 51 (range: 4 to 208) for 8 mg and 9 (range: 2 to 175) for 16 mg. Selatogrel was well tolerated, without major bleeding complications. Conclusions: Single-dose subcutaneous administration of selatogrel in patients with AMI was safe and induced a profound, rapid, and dose-related antiplatelet response.",

keywords = "P2Y, ST-segment elevation myocardial infarction, acute coronary syndrome, acute myocardial infarction, non–ST-segment elevation myocardial infarction, subcutaneous",

author = "Peter Sinnaeve and Gregor Fahrni and Dan Schelfaut and Alessandro Spirito and Christian Mueller and Frenoux, \{Jean Marie\} and Abdel Hmissi and Corine Bernaud and Mike Ufer and Tiziano Moccetti and Shaul Atar and Marco Valgimigli",

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month = may,

day = "26",

doi = "10.1016/j.jacc.2020.03.059",

language = "אנגלית",

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Sinnaeve, P, Fahrni, G, Schelfaut, D, Spirito, A, Mueller, C, Frenoux, JM, Hmissi, A, Bernaud, C, Ufer, M, Moccetti, T, Atar, S & Valgimigli, M 2020, 'Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction', Journal of the American College of Cardiology, vol. 75, no. 20, pp. 2588-2597. https://doi.org/10.1016/j.jacc.2020.03.059

TY - JOUR

T1 - Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction

AU - Sinnaeve, Peter

AU - Fahrni, Gregor

AU - Schelfaut, Dan

AU - Spirito, Alessandro

AU - Mueller, Christian

AU - Frenoux, Jean Marie

AU - Hmissi, Abdel

AU - Bernaud, Corine

AU - Ufer, Mike

AU - Moccetti, Tiziano

AU - Atar, Shaul

AU - Valgimigli, Marco

PY - 2020/5/26

Y1 - 2020/5/26

N2 - Background: Oral P2Y12 receptor antagonists exhibit delayed onset of platelet inhibition in patients with acute myocardial infarction (AMI). Selatogrel is a potent, highly selective, and reversible P2Y12 receptor antagonist with a rapid onset and short duration of action. Objectives: This study sought to assess inhibition of platelet aggregation following subcutaneous administration of selatogrel in patients with AMI. Methods: Patients with AMI were randomized to a single subcutaneous dose of selatogrel of 8 or 16 mg. The primary endpoint was response to treatment (P2Y12 reaction units <100; measured by VerifyNow) at 30 min post-dose. Safety was assessed up to 48 h post-injection. Results: Forty-seven patients received selatogrel 8 mg (n = 24) or 16 mg (n = 23) followed by ticagrelor (n = 43) or clopidogrel (n = 1). The proportion of responders 30 min post-dose was 91% (one-sided 97.5% confidence interval [CI]: 80% to 100%) and 96% (97.5% CI: 87% to 100%) with 8 and 16 mg, respectively (p values for responders >85% target; p = 0.142 and p = 0.009, respectively). Response rates were independent from type of AMI presentation, age, or sex. A similar response rate was observed at 15 min (8 mg: 75% [97.5% CI: 58% to 100%]; 16 mg: 91% [97.5% CI: 80% to 100%]), which was sustained at 60 min post-dose (8 mg: 75% [97.5% CI: 58% to 100%]; 16 mg: 96% [97.5% CI: 87% to 100%]). At 15 min, median P2Y12 reaction units was 51 (range: 4 to 208) for 8 mg and 9 (range: 2 to 175) for 16 mg. Selatogrel was well tolerated, without major bleeding complications. Conclusions: Single-dose subcutaneous administration of selatogrel in patients with AMI was safe and induced a profound, rapid, and dose-related antiplatelet response.

AB - Background: Oral P2Y12 receptor antagonists exhibit delayed onset of platelet inhibition in patients with acute myocardial infarction (AMI). Selatogrel is a potent, highly selective, and reversible P2Y12 receptor antagonist with a rapid onset and short duration of action. Objectives: This study sought to assess inhibition of platelet aggregation following subcutaneous administration of selatogrel in patients with AMI. Methods: Patients with AMI were randomized to a single subcutaneous dose of selatogrel of 8 or 16 mg. The primary endpoint was response to treatment (P2Y12 reaction units <100; measured by VerifyNow) at 30 min post-dose. Safety was assessed up to 48 h post-injection. Results: Forty-seven patients received selatogrel 8 mg (n = 24) or 16 mg (n = 23) followed by ticagrelor (n = 43) or clopidogrel (n = 1). The proportion of responders 30 min post-dose was 91% (one-sided 97.5% confidence interval [CI]: 80% to 100%) and 96% (97.5% CI: 87% to 100%) with 8 and 16 mg, respectively (p values for responders >85% target; p = 0.142 and p = 0.009, respectively). Response rates were independent from type of AMI presentation, age, or sex. A similar response rate was observed at 15 min (8 mg: 75% [97.5% CI: 58% to 100%]; 16 mg: 91% [97.5% CI: 80% to 100%]), which was sustained at 60 min post-dose (8 mg: 75% [97.5% CI: 58% to 100%]; 16 mg: 96% [97.5% CI: 87% to 100%]). At 15 min, median P2Y12 reaction units was 51 (range: 4 to 208) for 8 mg and 9 (range: 2 to 175) for 16 mg. Selatogrel was well tolerated, without major bleeding complications. Conclusions: Single-dose subcutaneous administration of selatogrel in patients with AMI was safe and induced a profound, rapid, and dose-related antiplatelet response.

KW - P2Y

KW - ST-segment elevation myocardial infarction

KW - acute coronary syndrome

KW - acute myocardial infarction

KW - non–ST-segment elevation myocardial infarction

KW - subcutaneous

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DO - 10.1016/j.jacc.2020.03.059

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C2 - 32439008

AN - SCOPUS:85084520176

SN - 0735-1097

VL - 75

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EP - 2597

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 20

ER -

Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction

Abstract

Bibliographical note

Funding

Keywords

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