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Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC) SCAI Clinical Expert Consensus Statement on Cardiogenic Shock Trends and Impact of Door-to-Balloon Time on Clinical Outcomes in Patients Aged <75, 75 to 84, and ≥85 Years With ST-Elevation Myocardial Infarction Astro-CHARM, the First 10-year ASCVD Risk Estimator Incorporating Coronary Calcium Contemporary Antiplatelet Pharmacotherapy in the Management of Acute Coronary Syndromes Non-eligibility for reperfusion therapy in patients presenting with ST-segment elevation myocardial infarction: Contemporary insights from the National Cardiovascular Data Registry (NCDR) Outcomes After Left Main Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting According to Lesion Site: Results From the EXCEL Trial
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Original ResearchVolume 75, Issue 20, May 2020

JOURNAL：JACC Article Link

Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction

P Sinnaeve, G Fahrni, M Valgimigli et al. Keywords: ACS; AMI; NSTEMI; P2Y12; STEMI; subcutaneous

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. (A Medical Research Study to Evaluate the Effects of ACT-246475 in Adults With Heart Attack; NCT03487445, 2018-000765-36 [EudraCT])

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