Effect of Alirocumab Added to High-Intensity Statin on Platelet Reactivity and Non-coding RNAs in AMI Patients: A Substudy of the PACMAN-AMI Trial

Objective: The effect of the PCSK9 inhibitor alirocumab on platelet aggregation among patients with acute myocardial infarction (AMI) remains unknown. We aimed to explore the effect of alirocumab added to high-intensity statin therapy on P2Y12 reaction unit (PRU) among AMI patients receiving dual antiplatelet therapy (DAPT) with a potent P2Y12 inhibitor (ticagrelor or prasugrel). In addition, we assessed circulating platelet-derived non-coding RNAs (microRNAs and YRNAs). Methods: This was a pre-specified, powered, pharmacodynamic substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150mg) versus placebo in AMI patients undergoing percutaneous coronary intervention. Patients recruited at Bern University Hospital, receiving DAPT with a potent P2Y12 inhibitor, and adherent to the study drug (alirocumab or placebo) were analyzed for the current study. The primary endpoint was PRU at 4 weeks after study drug initiation as assessed by VerifyNow P2Y12 point-of-care assays. Results: Among 139 randomized patients, the majority of patients received ticagrelor DAPT at 4 weeks (57 [86.4%] in the alirocumab group vs. 69 [94.5%] in the placebo group, P=0.14). There were no significant differences in the primary endpoint PRU at 4 weeks between groups (12.5 [IQR, 27.0] vs. 19.0 [IQR, 30.0], P=0.26). Consistent results were observed in 126 patients treated with ticagrelor (13.0 [IQR, 20.0] vs. 18.0 [IQR, 27.0], P=0.28). Similarly, platelet-derived non-coding RNAs did not significantly differ between groups. Conclusions: Among AMI patients receiving DAPT with a potent P2Y12 inhibitor, alirocumab had no significant effect on platelet reactivity as assessed by PRU and platelet-derived non-coding RNAs.