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.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.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.

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