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Thromb Haemost 2024; 124(06): 517-527
DOI: 10.1055/a-2156-7872
Cellular Haemostasis and Platelets

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

Yasushi Ueki 
1   Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland
,
Jonas D. Häner
1   Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland
,
Sylvain Losdat
2   CTU Bern, University of Bern, Bern, Switzerland
,
Giuseppe Gargiulo
1   Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland
3   Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy
,
Hiroki Shibutani
1   Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland
,
Sarah Bär
1   Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland
,
Tatsuhiko Otsuka
1   Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland
,
Raminta Kavaliauskaite
1   Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland
,
Vera R. Mitter
4   Institute of Hospital Pharmacy, Bern University Hospital, Bern, Switzerland
,
Fabrice Temperli
1   Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland
,
David Spirk
5   Department of Pharmacology, Bern University, Bern and Sanofi, Switzerland
,
Stefan Stortecky
1   Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland
,
George C. M. Siontis
1   Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland
,
Marco Valgimigli
6   Cardiocentro Ticino, Institute and Università della Svizzera Italiana (USI), Lugano, Switzerland
,
Stephan Windecker
1   Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland
,
Clemens Gutmann
7   King's British Heart Foundation Centre, King's College London, London, United Kingdom
8   Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Konstantinos C. Koskinas
1   Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland
,
Manuel Mayr
6   Cardiocentro Ticino, Institute and Università della Svizzera Italiana (USI), Lugano, Switzerland
7   King's British Heart Foundation Centre, King's College London, London, United Kingdom
,
Lorenz Räber
1   Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland
› Institutsangaben
Funding This study was supported by a research grant from Bern University Hospital.
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The Lipid–Platelet Interplay: Unraveling the Effects of PCSK9 Inhibition on Platelet ReactivityThromb Haemost 2024; 124(06): 528-532
DOI: 10.1055/s-0044-1782161

Abstract

Objective The effect of the PCSK9 (proprotein convertase subtilisin/kexin type 9) 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 noncoding RNAs (microRNAs and YRNAs).

Methods This was a prespecified, powered, pharmacodynamic substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) 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 [interquartile range, 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 noncoding RNAs did not significantly differ between groups.

Conclusion 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 noncoding RNAs.

Keywords

acute myocardial infarction - percutaneous coronary intervention - platelet reactivity - proprotein convertase subtilisin/kexin type 9 - microRNA

Supplementary Material



Publikationsverlauf

Eingereicht: 29. April 2023

Angenommen: 17. August 2023

Accepted Manuscript online:
18. August 2023

Artikel online veröffentlicht:
11. September 2023

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