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Effects of alirocumab on endothelial function and coronary atherosclerosis in myocardial infarction: A PACMAN-AMI
Emrush Rexhaj1, Sarah Bär1, Rodrigo Soria1
1Department of Cardiology, Bern University Hospital Inselspital, Freiburgstrasse 18, 3010, Bern, Switzerland.
Insights
Adding alirocumab to high-intensity statin therapy did not improve endothelial function (FMD) in acute myocardial infarction patients. FMD correlated with baseline plaque burden but not lipid pool or fibrous cap thickness.
Area of Science:
- Cardiology
- Vascular Biology
- Pharmacology
Background:
- Endothelial function, assessed by flow-mediated dilation (FMD), is crucial in cardiovascular health.
- The impact of protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on FMD in acute myocardial infarction (AMI) patients remains unclear.
- High-intensity statin therapy is a cornerstone of secondary prevention after AMI.
Purpose of the Study:
- To investigate the effect of the PCSK9 inhibitor alirocumab, added to high-intensity statin, on FMD in AMI patients.
- To explore the association between FMD and coronary atherosclerosis in non-infarct related arteries.
- To utilize advanced intracoronary imaging techniques (IVUS, NIRS, OCT) for detailed plaque analysis.
Main Methods:
- A substudy of the randomized-controlled PACMAN-AMI trial involving patients treated with alirocumab or placebo plus rosuvastatin.
- Brachial artery FMD measurements at 4 and 52 weeks.
- Intracoronary imaging (IVUS, NIRS, OCT) performed at baseline and 52 weeks for plaque characterization.
Main Results:
- No significant difference in FMD at 52 weeks between the alirocumab and placebo groups (5.44% vs. 5.45%).
- FMD significantly improved over 52 weeks in both groups.
- Early FMD (4 weeks) was associated with baseline plaque burden (IVUS) but not with lipid pool (NIRS) or fibrous cap thickness (OCT).
Conclusions:
- In AMI patients, adding alirocumab to high-intensity statin therapy did not enhance FMD compared to statin therapy alone.
- FMD is linked to the overall burden of coronary plaque but not specifically to lipid content or fibrous cap stability.
- These findings suggest that PCSK9 inhibition may not directly improve endothelial function in this patient population beyond standard statin therapy.
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.
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