Prasugrel Versus Ticagrelor in Patients With CYP2C19 Loss-of-Function Genotypes: Results of a Randomized Pharmacodynamic Study in a Feasibility Investigation of Rapid Genetic Testing

Francesco Franchi, Fabiana Rollini, Jose Rivas, Andrea Rivas, Malhar Agarwal, Maryuri Briceno, Mustafa Wali, Ahmed Nawaz, Gabriel Silva, Zubair Shaikh, Naji Maailiki, Latonya Been, Andres M Pineda, Siva Suryadevara, Daniel Soffer, Martin M Zenni, Theodore A Bass, Dominick J Angiolillo, Francesco Franchi, Fabiana Rollini, Jose Rivas, Andrea Rivas, Malhar Agarwal, Maryuri Briceno, Mustafa Wali, Ahmed Nawaz, Gabriel Silva, Zubair Shaikh, Naji Maailiki, Latonya Been, Andres M Pineda, Siva Suryadevara, Daniel Soffer, Martin M Zenni, Theodore A Bass, Dominick J Angiolillo

Abstract

The feasibility of rapid genetic testing in patients undergoing percutaneous coronary intervention (PCI) and the comparison of the pharmacodynamic effects of prasugrel versus ticagrelor among carriers of cytochrome P450 2C19 loss-of-function alleles treated with PCI has been poorly explored. Rapid genetic testing using the Spartan assay was shown to be feasible and provides results in a timely fashion in a real-world setting of patients undergoing coronary angiography (n = 781). Among patients (n = 223, 28.5%), carriers of at least 1 loss-of-function allele treated with PCI (n = 65), prasugrel, and ticagrelor achieve similar levels of platelet inhibition. (A Pharmacodynamic Study Comparing Prasugrel Versus Ticagrelor in Patients Undergoing PCI With CYP2C19 Loss-of-function [NCT02065479]).

Keywords: ACS, acute coronary syndrome; CI, confidence interval; CYP, cytochrome P450; DAPT, dual antiplatelet therapy; HPR, high on-treatment platelet reactivity; LOF, loss of function; PCI, percutaneous coronary intervention; PD, pharmacodynamic; PRU, P2Y12 reaction unit; genotyping; percutaneous coronary intervention; pharmacodynamics; prasugrel; ticagrelor.

© 2020 The Authors.

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
Study Design bid = twice a day; LD = loading dose; LHC = left heart catheterization; LOF = loss of function; MD = maintenance dose; PCI = percutaneous coronary intervention; PD = pharmacodynamics; qd = every day.
Figure 2
Figure 2
Trial Profile CABG = coronary artery bypass graft; CAD = coronary artery disease; CYP = cytochrome P450; GPI = glycoprotein IIb/IIIa inhibitor; LOF = loss of function; PCI = percutaneous coronary intervention.
Figure 3
Figure 3
Pharmacodynamic Assessment Measured by VerifyNow P2Y12 After Administration of Prasugrel Versus Ticagrelor The main figure represents P2Y12 reaction units (PRUs) measured by the VerifyNow P2Y12 assay. Values are expressed as means. Error bars indicate SDs; p values indicate the comparisons for superiority between groups at each time point. The box represents the primary endpoint: 24-h PRU absolute difference and 2-sided 95% confidence interval between prasugrel and ticagrelor. Tinted area indicates zone of noninferiority (NI). The dotted line represents the prespecified limit of noninferiority of +40.
Figure 4
Figure 4
Individual Values of Platelet Reactivity Measured by VerifyNow P2Y12 After Administration of Prasugrel Versus Ticagrelor Comparisons of P2Y12 reaction units (PRUs) measured by the VerifyNow P2Y12 assay. Data are presented as individual values. The dashed line indicates threshold for high on-treatment platelet reactivity. Solid lineswith error bars indicate mean ± SD. HPR = high on-treatment platelet reactivity.

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