Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction
Key result
Subcutaneous selatogrel achieves rapid 30-minute antiplatelet response in ~96% of AMI patients.
- P=0.009 (16 mg) and 0.142 (8 mg) for >85% target
- n=47
Why the study?
Does subcutaneous selatogrel provide rapid and effective platelet inhibition in patients with acute myocardial infarction?
Key Points
- To assess the pharmacodynamic response, speed of onset, and safety of subcutaneous selatogrel in patients presenting with acute myocardial infarction.
- Multicenter, randomized, double-blind, placebo-controlled phase 2 trial conducted in patients presenting with acute myocardial infarction.
- Participants received a single subcutaneous injection of selatogrel (8 mg or 16 mg) or matching placebo.
- Platelet reactivity was serially measured using point-of-care P2Y12 reaction units to determine inhibition onset and duration.
- Subcutaneous selatogrel achieved profound platelet inhibition within 15 to 30 minutes following administration across both active dose groups.
- Platelet inhibition was sustained for several hours before gradual recovery, with no drug-related major bleeding events observed.
Study Design
Type
RCT (n=47)
Randomization
Randomized
Structured PICO
Does subcutaneous selatogrel provide rapid and effective platelet inhibition in patients with acute myocardial infarction?
P
Population
47 patients with acute myocardial infarction randomized to a single subcutaneous dose of selatogrel 8 or 16 mg, with safety assessed up to 48 hours.
I
Intervention
Single subcutaneous dose of selatogrel 16 mg
C
Comparator
Single subcutaneous dose of selatogrel 8 mg
O
Outcome
Response to treatment (P2Y12 reaction units <100; measured by VerifyNow) at 30 min post-dosesurrogate
Main Result
Absolute Event Rate: 96% vs 91%
p-value: p=0.009 (16 mg) and 0.142 (8 mg) for >85% target
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Selatogrel, a new parenteral subcutaneous P2Y12 inhibitor, has also been developed for this purpose. Yet, unlike RUC-4, this treatment is meant to be self-administered by the patient at the time of symptom onset, which offers obvious advantages in terms of treatment delay but may carry the risks associated with self-administration.”
“From the moment that symptoms start, the clock is ticking. Thrombus formation is progressing, and ischemia is rapidly causing irreversible damage to the heart. In the initial stages of thrombus formation, platelet aggregation dominates – a process in which the platelet P2Y12 receptor plays a key role. If left untreated, the thrombus will become fibrin rich, at which point platelets have a more limited role in thrombus formation. This suggests that a fast-acting P2Y12 receptor antagonist could cut short the thrombus formation in the initial stages of thrombus formation. Our drug discovery team has created a compound with unique properties which might fill this important therapeutic gap.”
DLDeepak L. BhattInterventional cardiologist, Brigham and Women's Hospital
“P2Y12 receptor antagonists have been used in the treatment of millions of patients globally, and their safety and efficacy profiles are well established. Despite the success of chronic treatment with this class and other effective interventions, patients are still suffering recurrent heart attacks. The idea for patients to self-inject early in the onset of symptoms is truly innovative. The subcutaneous route of administration could overcome the onset delay observed with oral compounds from the same class.”
Implication
Single-dose subcutaneous selatogrel induces rapid and profound platelet inhibition in patients with AMI, offering a potential strategy to overcome the delayed onset of oral P2Y12 inhibitors.
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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Cite This Study
Sinnaeve et al. (2020) conducted an RCT in Acute Myocardial Infarction (n=47). Selatogrel vs. Selatogrel 8 mg was evaluated on Response to treatment (P2Y12 reaction units <100) at 30 min post-dose (p=0.009 (16 mg) and 0.142 (8 mg) for >85% target). A single subcutaneous dose of selatogrel or in patients with acute myocardial infarction achieved a rapid antiplatelet response at 30 minutes in 96% and 91% of patients, respectively.