Effects of lignocaine vs. opioids on antiplatelet activity of ticagrelor: The LOCAL trial

Himawan Fernando, Thy Duong, Kevin Huynh, Jonathan Noonan, James Shaw, Stephen J. Duffy, Ziad Nehme, Karen Smith, Paul S. Myles, Peter J. Meikle, Karlheinz Peter, Dion Stub

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5 Citations (Scopus)

Abstract

Aims: We assessed the impact of intravenous fentanyl and lignocaine on the pharmacokinetics and pharmacodynamics of ticagrelor in patients with unstable angina and non-ST-elevation myocardial infarction and their procedural analgesic efficacy and safety. Methods and results: Seventy patients undergoing coronary angiography with ticagrelor loading were included in the pharmacokinetic and pharmacodynamic analyses of this randomized trial. Plasma ticagrelor levels 2 h post-loading dose were significantly lower in the fentanyl arm than in the lignocaine treatment arm (598 vs. 1008 ng/mL, P = 0.014). The area under the plasma-time curves for ticagrelor (1228 vs. 2753 ng h/mL, P < 0.001) and its active metabolite (201 vs. 447 ng h/mL, P = 0.001) were both significantly lower in the fentanyl arm. Expression of activated platelet glycoprotein IIb/IIIa receptor (2829 vs. 1426 mean fluorescence intensity, P = 0.006) and P-selectin (439 vs. 211 mean fluorescence intensity, P = 0.001) was significantly higher at 60 min in the fentanyl arm. A higher proportion of patients had high on-treatment platelet reactivity in the fentanyl arm at 60 min using the Multiplate Analyzer (41% vs. 9%, P = 0.002) and 120 min using the VerifyNow (30% vs. 3%, P = 0.003) and VASP (37% vs. 6%, P = 0.002) assays. Both drugs were well tolerated with a high level of patient satisfaction. Conclusions: Unlike fentanyl, lignocaine does not impair the bioavailability or delay the antiplatelet effect of ticagrelor. Both drugs were well tolerated and effective with a high level of patient satisfaction for procedural analgesia. Routine procedural analgesia during percutaneous coronary intervention should be reconsidered and if performed, lignocaine is a beneficial alternative to fentanyl.

Original languageEnglish
Pages (from-to)4025-4036
Number of pages12
JournalEuropean Heart Journal
Volume42
Issue number39
DOIs
Publication statusPublished - 14 Oct 2021

Keywords

  • Acute coronary syndromes
  • Analgesia
  • Opioid-P2Yinhibitor interaction
  • Oral P2Yinhibitor treatment failure
  • Pharmacokinetics
  • Platelet reactivity

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