Impact of opioids on P2Y12 receptor inhibition in patients with ST-elevation myocardial infarction who are pre-treated with crushed ticagrelor: Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME 3) trial.

Abstract

AIMS:

Platelet inhibition induced by P2Y12 receptor antagonists in patients with ST-elevation myocardial infarction (STEMI) can be affected by concomitant use of opioids. The aim of this trial was to examine the effect of intravenous (iv) acetaminophen compared with iv fentanyl on P2Y12 receptor inhibition in patients with STEMI.

METHODS AND RESULTS:

The Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME 3) trial randomized 195 STEMI patients who were scheduled to undergo primary percutaneous coronary intervention (PCI) and were pre-treated with crushed ticagrelor to iv acetaminophen (N = 98) or iv fentanyl (N = 97) in the ambulance. The primary endpoint, consisting of the level of platelet reactivity units (PRU) measured immediately after primary PCI, was not significantly different between the study arms [median PRU 104 (IQR 37-215) vs. 175 (63-228), P = 0.18]. However, systemic levels of ticagrelor were significantly higher in the acetaminophen arm at the start of primary PCI [151 ng/mL (32-509) vs. 60 ng/mL (13-206), P = 0.007], immediately after primary PCI [326 ng/mL (94-791) vs. 115 ng/mL (38-326), P = 0.002], and at 1 h after primary PCI [488 ng/mL (281-974) vs. 372 ng/mL (95-635), P = 0.002]. Acetaminophen resulted in the same extent of pain relief when compared with fentanyl [reduction of 3 points on 10-step-pain scale before primary PCI (IQR 1-5)] in both study arms (P = 0.67) and immediately after PCI [reduction of 5 points (3-7); P = 0.96].

CONCLUSION:

The iv acetaminophen in comparison with iv fentanyl was not associated with significantly lower platelet reactivity in STEMI patients but resulted in significantly higher ticagrelor plasma levels and was effective in pain relief.

• Authors: Anne H Tavenier, Renicus S Hermanides, Jan Paul Ottervanger, Rudolf Tolsma, Antony van Beurden, Robbert Jan Slingerland, Peter G J Ter Horst, A T Marcel Gosselink, Jan-Henk E Dambrink, Maarten A H van Leeuwen, Vincent Roolvink, Elvin Kedhi, Olaf H Klungel, Svetlana V Belitser, Dominick J Angiolillo, Tobias Pustjens, Saman Rasoul, Ben Gho, Mera Stein, Lex Ruiters, Arnoud W J van 't Hof
• Journal: European heart journal. Cardiovascular pharmacotherapy (Eur Heart J Cardiovasc Pharmacother) Vol. 8 Issue 1 Pg. 4-12 (01 05 2022) ISSN: 2055-6845 [Electronic] England
• PMID: 32730628 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Chemical References

• Analgesics, Opioid
• Platelet Aggregation Inhibitors
• Purinergic P2Y Receptor Antagonists
• Ticagrelor

Topics

• Analgesics, Opioid (adverse effects)
• Humans
• Myocardial Infarction
• Percutaneous Coronary Intervention
• Platelet Aggregation Inhibitors
• Purinergic P2Y Receptor Antagonists
• ST Elevation Myocardial Infarction (diagnosis, therapy)
• Ticagrelor (therapeutic use)