Himawan Fernando1,2,3,4, Thy Duong2, Kevin Huynh2, Jonathan Noonan2,5, James Shaw1,2,3, Stephen J Duffy1,2,6, Ziad Nehme3,7, Karen Smith3,7, Paul S Myles3,8, Peter J Meikle2,3,5, Karlheinz Peter1,2,5, Dion Stub1,2,3,9. 1. Department of Cardiology, Alfred Hospital, 55 Commercial Road, Melbourne, Victoria 3004, Australia. 2. Baker Heart and Diabetes Institute, 75 Commercial Rd, Melbourne, Victoria 3004, Australia. 3. Monash University, Wellington Road, Melbourne, Victoria 3800, Australia. 4. Department of Cardiology, Bendigo Health, 100 Barnard St, Bendigo, Victoria 3550, Australia. 5. Department of Cardiometabolic Health, University of Melbourne, 75 Commercial Road, Melbourne, Victoria 3004, Australia. 6. Centre of Cardiovascular Research and Education in Therapeutics (CCRE), School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road Melbourne, Melbourne, Victoria 3004, Australia. 7. Centre for Research and Evaluation, Ambulance Victoria, PO Box 2000, Doncaster, Victoria 3108, Australia. 8. Department of Anaesthesiology and Perioperative Medicine, The Alfred and Monash University, 55 Commercial Road Melbourne, Melbourne, Victoria 3004, Australia. 9. Department of Cardiology, Western Health, 176 Furlong Rd, St Albans, Victoria 3021, Australia.
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. Published on behalf of the European Society of Cardiology. All rights reserved.
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. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Himawan Fernando; Ziad Nehme; Karlheinz Peter; Stephen Bernard; Michael Stephenson; Janet E Bray; Paul S Myles; Romi Stub; Peter Cameron; Andris H Ellims; Andrew J Taylor; David M Kaye; Karen Smith; Dion Stub Journal: Int J Cardiol Heart Vasc Date: 2021-11-08