Effects of alirocumab on endothelial function and coronary atherosclerosis in myocardial infarction: A PACMAN-AMI randomized clinical trial substudy.

Rexhaj, Emrush; Bär, Sarah; Soria, Rodrigo; Ueki, Yasushi; Häner, Jonas D; Otsuka, Tatsuhiko; Kavaliauskaite, Raminta; Siontis, George CM; Stortecky, Stefan; Shibutani, Hiroki; Spirk, David; Engstrøm, Thomas; Lang, Irene; Morf, Laura; Ambühl, Maria; Windecker, Stephan; Losdat, Sylvain; Koskinas, Konstantinos C; Räber, Lorenz (2024). Effects of alirocumab on endothelial function and coronary atherosclerosis in myocardial infarction: A PACMAN-AMI randomized clinical trial substudy. Atherosclerosis, 392, p. 117504. Elsevier 10.1016/j.atherosclerosis.2024.117504

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BACKGROUND AND AIMS

The effects of protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on endothelial function as assessed by flow-mediated dilation (FMD) in patients with acute myocardial infarction (AMI) are unknown. Therefore, we aimed to investigate the effects of the PCSK9 inhibitor alirocumab added to high-intensity statin on FMD, and its association with coronary atherosclerosis in non-infarct related arteries using intracoronary intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT).

METHODS

This was a pre-specified substudy among patients recruited at Bern University Hospital, Switzerland, for the randomized-controlled, double-blind, PACMAN-AMI trial, which compared the effects of biweekly alirocumab 150 mg vs. placebo added to rosuvastatin. Brachial artery FMD was measured at 4 and 52 weeks, and intracoronary imaging at baseline and 52 weeks.

RESULTS

139/173 patients completed the substudy. There was no difference in FMD at 52 weeks in the alirocumab (n = 68, 5.44 ± 2.24%) versus placebo (n = 71, 5.45 ± 2.19%) group (difference = -0.21%, 95% CI -0.77 to 0.35, p = 0.47). FMD improved throughout 52 weeks in both groups similarly (p < 0.001). There was a significant association between 4 weeks FMD and baseline plaque burden (IVUS) (n = 139, slope = -1.00, p = 0.006), but not with lipid pool (NIRS) (n = 139, slope = -7.36, p = 0.32), or fibrous cap thickness (OCT) (n = 81, slope = -1.57, p = 0.62).

CONCLUSIONS

Among patients with AMI, the addition of alirocumab did not result in further improvement of FMD as compared to 52 weeks secondary preventative medical therapy including high-intensity statin therapy. FMD was significantly associated with coronary plaque burden at baseline, but not with lipid pool or fibrous cap thickness.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
04 Faculty of Medicine > Pre-clinic Human Medicine > Department of Clinical Research (DCR)

UniBE Contributor:

Rexhaj, Emrush, Bär, Sarah, Soria Maldonado, Rodrigo, Ueki, Yasushi, Häner, Jonas, Otsuka, Tatsuhiko, Kavaliauskaite, Raminta, Siontis, Georgios, Stortecky, Stefan, Shibutani, Hiroki, Spirk, David, Ambühl, Maria, Windecker, Stephan, Losdat, Sylvain Pierre, Koskinas, Konstantinos, Räber, Lorenz

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1879-1484

Publisher:

Elsevier

Language:

English

Submitter:

Pubmed Import

Date Deposited:

27 Mar 2024 09:36

Last Modified:

14 May 2024 00:15

Publisher DOI:

10.1016/j.atherosclerosis.2024.117504

PubMed ID:

38513436

Uncontrolled Keywords:

Alirocumab Coronary atherosclerosis Endothelial function Flow-mediated dilation Intracoronary imaging PCSK9 inhibitor

BORIS DOI:

10.48350/194628

URI:

https://boris.unibe.ch/id/eprint/194628

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