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

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.