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Randomized Controlled Trial
. 2022 Jan 5;8(1):4-12.
doi: 10.1093/ehjcvp/pvaa095.

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

Anne H Tavenier, Renicus S Hermanides  1 , Jan Paul Ottervanger  1 , Rudolf Tolsma  2 , Antony van Beurden  3 , Robbert Jan Slingerland  4 , Peter G J Ter Horst  5 , A T Marcel Gosselink  1 , Jan-Henk E Dambrink  1 , Maarten A H van Leeuwen  1 , Vincent Roolvink  1 , Elvin Kedhi  6 , Olaf H Klungel  7 , Svetlana V Belitser  7 , Dominick J Angiolillo  8 , Tobias Pustjens  9   10 , Saman Rasoul  9   10 , Ben Gho  10 , Mera Stein  10 , Lex Ruiters  10 , Arnoud W J van 't Hof  1   9   10
Affiliations
Randomized Controlled Trial

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

Anne H Tavenier et al. Eur Heart J Cardiovasc Pharmacother. .

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.

Keywords: Acetaminophen; Fentanyl; Primary coronary intervention; ST-elevation myocardial infarction; Ticagrelor.

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Figures

Figure 1
Figure 1
Patient flow diagram. iv, intravenous.
Figure 2
Figure 2
(A) The platelet reactivity units are shown at different time points for fentanyl intravenously and acetaminophen intravenously. No statistically significant differences between both study arms were seen in platelet reactivity unit at T1 (pre-primary percutaneous coronary intervention; P = 0.08), at T2 (immediately after primary percutaneous coronary intervention; P = 0.18), at T3 (1 h after primary percutaneous coronary intervention; P = 0.18), and at T4 (6 h after primary percutaneous coronary intervention; P = 0.48). (B) The ticagrelor concentrations are shown at different time points for fentanyl iv and acetaminophen iv. Significant differences were seen at T1 (P = 0.007), T2 (P = 0.002), and T3 (P = 0.002), but not for T4 (P = 0.26).
Figure 3
Figure 3
Correlation figures between the median platelet reactivity units and ticagrelor concentrations at different time points. T1, before primary PCI; T2, immediately after primary PCI; T3, 1 h after primary PCI; T4, 6 h after primary PCI.
See this image and copyright information in PMC

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