Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:75

Article

Sinnaeve, Peter¹  Fahrni, Gregor²  Schelfaut, Dan³  Spirito, Alessandro⁴  Mueller, Christian^5,6  Frenoux, Jean-Marie⁷  Hmissi, Abdel⁷  Bernaud, Corine⁷  Ufer, Mike⁷  Moccetti, Tiziano⁸  Atar, Shaul^9,10  Valgimigli, Marco⁴ 

[1] Univ Hosp Leuven, Dept Cardiovasc Med, Leuven, Belgium

[2] Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland

[3] OLV Clin Aalst, Cardiovasc Ctr Aalst, Aalst, Belgium

[4] Univ Bern, Bern Univ Hosp, Dept Cardiol, Bern, Switzerland

[5] Univ Hosp Basel, Dept Cardiol, Basel, Switzerland

[6] Univ Hosp Basel, Cardiovasc Res Inst Basel, Basel, Switzerland

[7] Idorsia Pharmaceut Ltd, Allschwil, Switzerland

[8] Cardiol Cardioctr Ticino, Lugano, Switzerland

[9] Galilee Med Ctr, Dept Cardiol, Nahariyya, Israel

[10] Bar Ilan Univ, Azrieli Fac Med, Safed, Israel

关键词: acute coronary syndrome;    acute myocardial infarction;    non-ST-segment elevation myocardial infarction;    P2Y(12);    ST-segment elevation myocardial infarction;    subcutaneous;   

DOI  :  10.1016/j.jacc.2020.03.059

来源: Elsevier

【 摘 要 】

BACKGROUND Oral P2Y(12) receptor antagonists exhibit delayed onset of platelet inhibition in patients with acute myocardial infarction (AMI). Selatogrel is a potent, highly selective, and reversible P2Y(12) 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 (P2Y(12) 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 P2Y(12) 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. (A Medical Research Study to Evaluate the Effects of ACT246475 in Adults With Heart Attack; NCT03487445, 2018-000765-36 [EudraCT]) (C) 2020 Published by Elsevier on behalf of the American College of Cardiology Foundation.

【 授权许可】

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