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.

Ueki, Yasushi; Häner, Jonas; Losdat, Sylvain; Gargiulo, Giuseppe; Shibutani, Hiroki; Bär, Sarah; Otsuka, Tatsuhiko; Kavaliauskaite, Raminta; Mitter, Vera; Temperli, Fabrice; Spirk, David; Stortecky, Stefan; Siontis, George; Valgimigli, Marco; Windecker, Stephan; Gutmann, Clemens; Koskinas, Konstantinos C; Mayr, Manuel; Raber, Lorenz (2023). 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. (In Press). Thrombosis and haemostasis Thieme 10.1055/a-2156-7872

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
04 Faculty of Medicine
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology

UniBE Contributor:

Ueki, Yasushi, Häner, Jonas, Gargiulo, Giuseppe, Shibutani, Hiroki, Bär, Sarah, Otsuka, Tatsuhiko, Kavaliauskaite, Raminta, Mitter, Vera Ruth, Temperli, Fabrice Gil, Spirk, David, Stortecky, Stefan, Siontis, Georgios, Windecker, Stephan, Koskinas, Konstantinos, Räber, Lorenz

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2567-689X

Publisher:

Thieme

Language:

English

Submitter:

Pubmed Import

Date Deposited:

21 Aug 2023 12:10

Last Modified:

27 Sep 2023 14:02

Publisher DOI:

10.1055/a-2156-7872

PubMed ID:

37595625

BORIS DOI:

10.48350/185582

URI:

https://boris.unibe.ch/id/eprint/185582

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