Differential impact of fentanyl and morphine doses on ticagrelor-induced platelet inhibition in ST-segment elevation...

Area of Science:

• Cardiology
• Pharmacology
• Interventional Cardiology

Background:

• Patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) often receive opioids and antiplatelet agents like ticagrelor.
• The influence of opioid type and dose on ticagrelor's pharmacodynamic and pharmacokinetic response in STEMI patients remains incompletely understood.
• Previous findings indicated intravenous fentanyl did not enhance ticagrelor-induced platelet inhibition compared to morphine within 2 hours.

Purpose of the Study:

• To investigate the relationship between the total dose of intravenous fentanyl and morphine and ticagrelor's pharmacodynamic and pharmacokinetic effects.
• To analyze the impact of opioid dosage on platelet reactivity (PRU) and ticagrelor plasma levels in STEMI patients post-PCI.

Main Methods:

• A post-hoc subanalysis of the PERSEUS trial (NCT02531165) involving STEMI patients treated with primary PCI and ticagrelor pretreatment.
• Patients were stratified based on low vs. high total doses of received intravenous fentanyl or morphine.
• Platelet reactivity (PRU) at 2 hours and up to 12 hours, along with ticagrelor and its active metabolite plasma levels, were assessed.
• Generalized linear models were used to analyze the relationship between opioid doses and ticagrelor responses.

Main Results:

• A significant correlation was observed between both raw and weight-weighted doses of fentanyl and platelet reactivity (PRU) at 2 hours.
• Patients receiving lower doses of fentanyl exhibited significantly lower PRU at 2 hours compared to those receiving higher doses.
• No significant correlation was found between morphine dose and PRU, nor significant differences in PRU between low and high morphine dose groups.
• Weight-weighted doses of both fentanyl and morphine correlated with plasma levels of ticagrelor and its active metabolite at 2 hours.

Conclusions:

• A dose-dependent relationship exists between intravenous fentanyl administration and ticagrelor-induced platelet inhibition in STEMI patients undergoing primary PCI.
• Morphine dosage did not demonstrate a similar dose-dependent effect on ticagrelor-induced platelet inhibition in this patient cohort.
• These findings highlight the differential impact of opioids on antiplatelet therapy efficacy in STEMI management.