Abstract
AIMS : To study the pharmacodynamics and pharmacokinetics of selatogrel, a novel P2Y12 receptor antagonist for subcutaneous administration, in patients with chronic coronary syndromes (CCS).
METHODS AND RESULTS : In this double-blind, randomized study of 345 patients with CCS on background oral antiplatelet therapy, subcutaneous selatogrel (8 mg, n = 114; or 16 mg, n = 115) was compared with placebo (n = 116) (ClinicalTrials.gov: NCT03384966). Platelet aggregation was assessed over 24 h (VerifyNow assay) and 8 h (light transmittance aggregometry; LTA). Pharmacodynamic responders were defined as patients having P2Y12 reaction units (PRU) <100 at 30 min post-dose and lasting ≥3 h. At 30 min post-dose, 89% of patients were responders to selatogrel 8 mg, 90% to selatogrel 16 mg, and 16% to placebo (P < 0.0001). PRU values (mean ± standard deviation) were 10 ± 25 (8 mg), 4 ± 10 (16 mg), and 163 ± 73 (placebo) at 15 min and remained <100 up to 8 h for both doses, returning to pre-dose or near pre-dose levels by 24 h post-dose. LTA data showed similarly rapid and potent inhibition of platelet aggregation. Selatogrel plasma concentrations peaked ∼30 min post-dose. Selatogrel was safe and well-tolerated with transient dyspnoea occurring overall in 7% (16/229) of patients (95% confidence interval: 4-11%).
CONCLUSIONS : Selatogrel was rapidly absorbed following subcutaneous administration in CCS patients, providing prompt, potent, and consistent platelet P2Y12 inhibition sustained for ≥8 h and reversible within 24 h. Further studies of subcutaneous selatogrel are warranted in clinical scenarios where rapid platelet inhibition is desirable.
Original language | English |
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Article number | ehz807 |
Pages (from-to) | 3132-3140 |
Number of pages | 9 |
Journal | European Heart Journal |
Volume | 41 |
Issue number | 33 |
Early online date | 14 Nov 2019 |
DOIs | |
Publication status | Published - 1 Sept 2020 |
Keywords
- Selatogrel
- Platelet aggregation
- Coronary artery disease
- P2Y(12) receptor antagonist
- Pharmacodynamics
- Pharmacokinetics
- ELEVATION MYOCARDIAL-INFARCTION
- ANTIPLATELET THERAPY
- TICAGRELOR
- PRASUGREL
- CLOPIDOGREL
- INHIBITION
- DYSPNEA
- INTERVENTION
- ACT-246475
- MORPHINE