Impact of alirocumab added to high-intensity statin therapy on platelet function in AMI patients: a pre-specified substudy of the randomized, placebo-controlled PACMAN-AMI trial

Abstract Background Previous small observational studies have suggested a potential association of proprotein convertase subtilisin kexin type 9 (PCSK9) and platelet reactivity. However, the role of the PCSK9 inhibitor alirocumab on platelet aggregation among patients with acute myocardial infarction (AMI) remains unknown. Purpose We investigated the effect of alirocumab on P2Y12 reaction unit (PRU) on top of high-intensity statin therapy among AMI patients receiving dual antiplatelet therapy (DAPT) with a potent P2Y12 inhibitor (ticagrelor or prasugrel). Methods This was a pre-specified, powered, pharmacodynamic substudy nested within the PACMAN (effects of the PSCK9 antibody AliroCuMab on coronary Atherosclerosis in patieNts with Acute Myocardial Infarction) trial, a randomized, double-blind trial comparing biweekly alirocumab (150mg) versus placebo in AMI patients undergoing percutaneous coronary intervention (PCI). Patients recruited at Bern University Hospital, receiving DAPT with either ticagrelor or prasugrel at 4 weeks and adherent to the study drug (alirocumab or placebo) were analyzed for the current study. The VerifyNow P2Y12 point-of-care assays were used to measure PRU at baseline (i.e. before first study drug administration), 4 weeks, and 52 weeks after study drug administration (higher PRU levels indicating greater platelet aggregation). The primary endpoint was PRU at 4 weeks. Results Among 139 randomized patients (mean age 58.2 years [SD, 9.5], 21 [15.0%] women, mean LDL-C level 150.6mg/dL [SD, 30.9]), baseline characteristics were well balanced between groups including baseline PRU (50.0 [IQR, 120.0] in the alirocumab group vs. 62.0 [IQR, 122.0] in the placebo group, P=0.75). At 4 weeks, mean LDL-C was significantly lower in the alirocumab group (23.5 [SD, 23.7] mg/dL vs. 74.4 [SD, 30.5] mg/dL, P<0.001). The majority of patients received ticagrelor DAPT at 4 weeks (57 [86.4%] vs. 69 [94.5%], P=0.14). There were no significant differences in PRU at 4 weeks (12.5 [IQR, 27.0] vs. 19.0 [IQR, 30.0], P=0.26) and at 52 weeks (25.0 [IQR, 37.0] vs. 34.0 [IQR, 59.0], P=0.07) (Figure). Consistent results were observed in 126 patients treated with ticagrelor (i.e. after excluding 13 patients treated with prasugrel) at 4 weeks (13.0 [IQR, 20.0] vs. 18.0 [IQR, 27.0], P=0.28). Conclusion Among AMI patients receiving DAPT with potent P2Y12 inhibitors, alirocumab had no significant effect on platelet function as assessed by PRU. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Bern University Hospital