In a groundbreaking trial, alirocumab combined with statins not only shrinks coronary plaque but also transforms high-risk lesions into stable, heart-protecting phenotypes, offering new hope for reducing future cardiac events.
Study: Lesion-Level Effects of LDL-C–Lowering Therapy in Patients With Acute Myocardial Infarction. Image Credit: Rocos / Shutterstock
In a recent article published in the journal JAMA Cardiology, a team of European researchers investigated whether therapies aimed at lowering the levels of low-density lipoprotein cholesterol (LDL-C) had a positive impact on coronary lesions exhibiting advanced atherosclerotic features and could potentially lower the risk of future vascular events.
Background
The risk of cardiovascular disease related to atherosclerosis remains high despite substantial research on innovative diagnostic and therapeutic strategies. Numerous in vivo and ex vivo studies have revealed that mild atherosclerotic plaques in the arterial segments are often not treated at the time of a previous vascular event, causing the occurrence of acute atherothrombotic events in these segments due to the rapid progression of the plaques.
The arterial segments that are destabilized due to the rapid progression of these plaques, called coronary lesions, are responsible for incrementally increasing the risk of future cardiovascular events. Studies using intracoronary imaging have shown that therapies aimed at lowering the levels of lipids can decrease the lipid content and overall atherosclerosis burden in patients with coronary lesions.
However, most of the trials for these lipid-lowering therapies have analyzed entire vessels and not explicitly examined the impact of these treatments on the coronary segments with the most significant burden and risk of plaques.
About the study
In the present study, the researchers conducted a lesion-level analysis using the PACMAN-AMI trial, which assessed the effects of alirocumab, a proprotein convertase subtilisin/kexin type 9 antibody, on atherosclerosis in acute myocardial infarction patients.
The study aimed to compare the changes in atherosclerotic features after alirocumab or placebo was administered along with high-intensity statins to myocardial infarction patients with non-culprit coronary lesions.
The PACMAN-AMI was a placebo-controlled trial in which 300 patients were randomly selected to receive either alirocumab or the placebo along with high-intensity statin treatment. Baseline and follow-up assessments consisted of evaluations using optical coherence tomography (OCT), intravascular ultrasound (IVUS), and near-infrared spectroscopy (NIS).
The proximal regions of two arteries that were not related to the initial myocardial infarction but showed evidence during angiography of coronary atherosclerosis without obstructive disease were examined.
When three or more slices of coronary segments that were obtained consecutively showed a plaque burden of 40% or more in the IVUS images, these segments were categorized as coronary lesions. Segments with plaque burden that were separated by 5 mm or more were considered separate coronary lesions.
The study's primary endpoint was the change in percent atheroma volume as derived from the IVUS images, calculated between baseline and the 52-week follow-up. The two secondary outcomes examined in the study were the change in lipid core burden and fibrous cap thickness. The researchers also examined how the coronary lesions that had high-risk plaque features evolved between baseline and follow-up.
Results
The study found that the administration of intensive therapy for lowering lipid levels resulted in substantially greater percent atheroma volume regression in the coronary lesions than was previously described in studies that analyzed at the vessel level.
Furthermore, when statin therapy was combined with alirocumab, the minimum lumen area of the coronary lesions underwent significantly greater enlargement as compared to what was observed with statin therapy alone. The administration of alirocumab also resulted in a more significant number of high-risk plaque phenotypes transitioning into low-lipid and stable plaque phenotypes.
The effect of statin and alirocumab treatment at the lesional level was observed to be almost twice what was observed at the vessel level, with a 5% decrease in percent atheroma volume for the entire lesion, as well as a 10% decrease in percent atheroma volume for the overall plaque burden.
The researchers also found that the alirocumab treatment group experienced an increase in the number of fibrocalcific or fibrous lesions between baseline and follow-up as compared to the placebo group. The researchers attributed it to the association between alirocumab and more frequent reclassification of high-risk, lipid-rich lesions to non-lipid-rich, stable lesions in all the high-risk plaque phenotypes.
Conclusions
Overall, the study demonstrated that the impact of highly intensive lipid-lowering treatments for myocardial infarction patients with non-culprit coronary lesions was more apparent when the assessments were conducted at the level of the lesions rather than the vessels.
Furthermore, the addition of alirocumab, a lipid-lowering therapy, to the highly intensive statin treatment significantly increased the conversion of high-risk plaque phenotypes to stable, low-lipid plaque phenotypes.
Journal reference:
- Biccirè, Flavio G, Kakizaki, R., Koskinas, K.C., Ueki, Y., Häner, J., Shibutani, H., Lønborg, J., Spitzer, E., Iglesias, J.F., Otsuka, T., George, Stortecky, S., Kaiser, C., Ambühl, M., Morf, L., Ondracek, A.S., Geuns, van, Spirk, D., Daemen, J. & Mach, F. (2024) Lesion-Level Effects of LDL-C-Lowering Therapy in Patients With Acute Myocardial Infarction: A Post Hoc Analysis of the PACMAN-AMI Trial. JAMA Cardiology. DOI:10.1001/jamacardio.2024.3200, https://jamanetwork.com/journals/jamacardiology/fullarticle/2823382
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