Veno-arterial ECMO reduces ticagrelor clearance, with simulations supporting a reduced regimen of a 120-135 mg loading dose and 60 mg once daily to maintain target trough concentrations.
Does VA-ECMO alter the pharmacokinetics of ticagrelor in patients with acute coronary syndrome?
VA-ECMO substantially alters ticagrelor pharmacokinetics, providing model-informed support for a reduced once-daily dosing strategy in this high-risk population.
Absolute Event Rate: 0% vs 0%
Although patients with acute coronary syndrome supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO) have a high risk of thrombosis and bleeding, antiplatelet pharmacology in this setting is not well defined. This prospective observational study investigated the population pharmacokinetics of ticagrelor and its active metabolite AR-C124910XX and explored model-informed dosing strategies among this population. Paired pharmacokinetic sampling was performed at predefined time points during ON- and OFF-ECMO periods. Plasma concentrations were measured using a validated liquid chromatography-tandem mass spectrometry assay and analyzed with NONMEM to develop a joint parent-metabolite model and evaluate the effects of VA-ECMO status and flow rate on ticagrelor disposition. Monte Carlo simulations of various ECMO flow-rate scenarios examined alternative loading and maintenance regimens using prespecified trough concentrations of 180-360 ng/mL, as derived from previous exposure-response and exposure-bleeding analyses in non-ECMO populations. A total of 225 ticagrelor and 225 metabolite concentrations (127 ON-ECMO and 98 OFF-ECMO) from 20 patients were analyzed. VA-ECMO support was associated with reduced ticagrelor clearance and increased volume of distribution, while higher flow rates were associated with decreased volumes of distribution. In simulations, an initial loading dose of 120-135 mg followed by a 60 mg maintenance dose once daily most consistently maintained predicted trough concentrations within the target range during VA-ECMO, whereas 90 mg once daily frequently exceeded the upper bound. These findings indicate that VA-ECMO substantially altered ticagrelor pharmacokinetics and provided quantitative, model-informed support for reduced once daily dosing strategies; however, further pharmacokinetic-pharmacodynamic and outcome studies are needed to confirm these findings.
Kang et al. (Tue,) reported a other. Veno-arterial ECMO reduces ticagrelor clearance, with simulations supporting a reduced regimen of a 120-135 mg loading dose and 60 mg once daily to maintain target trough concentrations.