P2Y12 Inhibition in Patients Requiring Oral Anticoagulation after Percutaneous Coronary Intervention: The SWAP-AC-2 Study

Luis Ortega-Paz; Wilbert Bor; Francesco Franchi; Wout W A van de Broek; Fabiana Rollini; Salvatore Giordano; Mattia Galli; Latonya Been; Ghussan Ghanem; Awss Shalhoub; Haroutioun Garabedian; Tala Al Saleh; Ekin Uzunoglu; Xuan Zhou; Andrea Rivas; Andres M Pineda; Siva Suryadevara; Daniel Soffer; Madeline K Mahowald; Calvin Y Choi; Martin M Zenni; Fladia Phoenix; Ramzi A Ajjan; Jurrien M Ten Berg; Dominick J Angiolillo

doi:10.1016/j.jcin.2024.03.027

P2Y₁₂ Inhibition in Patients Requiring Oral Anticoagulation after Percutaneous Coronary Intervention: The SWAP-AC-2 Study

JACC Cardiovasc Interv. 2024 Apr 1:S1936-8798(24)00631-9. doi: 10.1016/j.jcin.2024.03.027. Online ahead of print.

Authors

Luis Ortega-Paz¹, Wilbert Bor², Francesco Franchi³, Wout W A van de Broek², Fabiana Rollini³, Salvatore Giordano³, Mattia Galli⁴, Latonya Been³, Ghussan Ghanem³, Awss Shalhoub³, Haroutioun Garabedian³, Tala Al Saleh³, Ekin Uzunoglu³, Xuan Zhou³, Andrea Rivas³, Andres M Pineda³, Siva Suryadevara³, Daniel Soffer³, Madeline K Mahowald³, Calvin Y Choi³, Martin M Zenni³, Fladia Phoenix⁵, Ramzi A Ajjan⁵, Jurrien M Ten Berg², Dominick J Angiolillo⁶

Affiliations

¹ Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA. Electronic address: https://twitter.com/Ortega_Paz.
² St. Antonius Hospital in Nieuwegein, The Netherlands.
³ Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA.
⁴ Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy.
⁵ Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
⁶ Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA. Electronic address: dominick.angiolillo@jax.ufl.edu.

PMID: 38597172
DOI: 10.1016/j.jcin.2024.03.027

Abstract

Background: Among patients treated with a novel oral anticoagulant (NOAC) undergoing percutaneous coronary intervention (PCI), combination therapy with clopidogrel (i.e., known as dual antithrombotic therapy [DAT]) is the treatment of choice. However, there are concerns for individuals with impaired response to clopidogrel.

Objectives: To assess the pharmacodynamic (PD) effects of clopidogrel vs. low-dose ticagrelor in patients with impaired clopidogrel response assessed by the ABCD-GENE score.

Methods: This was a prospective, randomized PD study of NOAC-treated patients undergoing PCI. Patients with an ABCD-GENE score ≥10 (n=39), defined as having impaired clopidogrel response, were randomized to low-dose ticagrelor (n=20; 60 mg/bid) or clopidogrel (n=19; 75 mg/qd). Patients with an ABCD-GENE<10 (n=42) were treated with clopidogrel (75 mg/qd; control cohort). PD assessments at baseline and 30 days post-randomization (trough and peak) were performed to assess P2Y₁₂ signaling [VerifyNow P2Y₁₂ reaction units (PRU), light transmittance aggregometry (LTA), and vasodilator-stimulated phosphoprotein (VASP)]; makers of thrombosis not specific to P2Y₁₂ signaling were also assessed. The primary endpoint was PRU (trough levels) at 30 days.

Results: At 30 days, PRU levels were reduced with ticagrelor-based DAT compared with clopidogrel-based DAT at trough (23.0 [3.0-46.0] vs. 154.5 [77.5-183.0]; p<0.001) and peak (6.0 [4.0-14.0] vs. 129.0 [66.0-171.0]; p<0.001). Trough PRU levels in the control arm (104.0 [35.0-167.0]) were higher than ticagrelor-based DAT (p=0.005) and numerically lower than clopidogrel-based DAT (p=0.234). Results were consistent by LTA and VASP. Markers measuring other pathways leading to thrombus formation were largely unaffected.

Conclusions: In NOAC-treated patients undergoing PCI with an ABCD-gene score ≥10, ticagrelor-based DAT using a 60 mg bid regimen reduced platelet P2Y₁₂ reactivity compared to clopidogrel-based DAT.

Keywords: anticoagulants; clopidogrel; coronary artery disease; percutaneous coronary intervention; pharmacodynamic; platelets; ticagrelor.