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Lesion-Level Effects of LDL-C-Lowering Therapy in Patients With Acute Myocardial Infarction: A Post Hoc Analysis of
Flavio G Biccirè1, Ryota Kakizaki1, Konstantinos C Koskinas1
1Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland.
Insights
Very intensive lipid-lowering therapy with alirocumab significantly reduced atherosclerotic plaque volume and promoted plaque stabilization. This lesion-level analysis shows greater regression and improved plaque phenotypes compared to statin therapy alone.
Area of Science:
- Cardiovascular Medicine
- Interventional Cardiology
- Pharmacology
Background:
- Previous studies on lipid-lowering therapy focused on vessel-level changes, irrespective of plaque burden.
- Understanding therapy effects on advanced atherosclerotic lesions is crucial for predicting future cardiovascular events.
Purpose of the Study:
- To investigate the impact of alirocumab plus high-intensity statin therapy on coronary lesions with advanced atherosclerotic features.
- To assess lesion-level changes in plaque volume and high-risk plaque characteristics.
Main Methods:
- Post hoc analysis of the PACMAN-AMI randomized clinical trial.
- Inclusion of nonculprit lesions (plaque burden ≥40%) identified by intravascular ultrasound (IVUS).
- Utilized IVUS, near-infrared spectroscopy, and optical coherence tomography for imaging at baseline and 52-week follow-up.
- Manual matching of images by blinded readers.
Main Results:
- Alirocumab significantly reduced percent atheroma volume (PAV) (-4.86% vs -2.78%, P<.001) and PAV at the minimum lumen area (MLA) site (-10.14% vs -6.70%, P<.001).
- MLA increased with alirocumab (0.15 mm²) compared to a decrease with placebo (-0.07 mm², P=.04).
- Alirocumab promoted a transition to less lipid-rich plaque phenotypes (61.8% vs 41.8%, P=.03) and more stable fibrous/fibrocalcific phenotypes in thin-cap fibroatheromas (30.8% vs 8.1%, P=.02).
Conclusions:
- At the lesion level, alirocumab plus statin therapy induced greater plaque regression than statin therapy alone.
- Treatment with alirocumab led to increased lesion MLA and a more frequent shift towards stable plaque phenotypes.
- These findings highlight the benefit of intensive lipid-lowering therapy in stabilizing high-risk coronary atherosclerotic lesions.
Importance:
Previous studies investigated atherosclerotic changes induced by lipid-lowering therapy in extensive coronary segments irrespective of baseline disease burden (a vessel-level approach).
Objective:
To investigate the effects of lipid-lowering therapy on coronary lesions with advanced atherosclerotic plaque features and presumably higher risk for future events.
Design, Setting, And Participants:
The PACMAN-AMI randomized clinical trial (enrollment: May 2017 to October 2020; final follow-up: October 2021) randomized patients with acute myocardial infarction to receive alirocumab or placebo in addition to high-intensity statin therapy. In this post hoc lesion-level analysis, nonculprit lesions were identified as segments with plaque burden 40% or greater defined by intravascular ultrasound (IVUS). IVUS, near-infrared spectroscopy, and optical coherence tomography images at baseline and the 52-week follow-up were manually matched by readers blinded to treatment allocation. Data for this study were analyzed from October 2022 to November 2023.
Interventions:
Alirocumab or placebo in addition to high-intensity statin therapy.
Main Outcomes And Measures:
Lesion-level imaging outcome measures, including high-risk plaque characteristics and phenotypes.
Results:
Of the 245 patients in whom lesions were found, 118 were in the alirocumab group (mean [SD] age, 58.2 [10.0] years; 101 [85.6%] male and 17 [14.4%] female) and 127 in the placebo group (mean [SD] age, 57.7 [8.8] years; 104 [81.9%] male and 23 [18.1%] female). Overall, 591 lesions were included: 287 lesions (118 patients, 214 vessels) in the alirocumab group and 304 lesions (127 patients, 239 vessels) in the placebo group. Lesion-level mean change in percent atheroma volume (PAV) was -4.86% with alirocumab vs -2.78% with placebo (difference, -2.02; 95% CI, -3.00 to -1.05; P < .001). At the minimum lumen area (MLA) site, mean change in PAV was -10.14% with alirocumab vs -6.70% with placebo (difference, -3.36; 95% CI, -4.98 to -1.75; P < .001). MLA increased by 0.15 mm2 with alirocumab and decreased by 0.07 mm2 with placebo (difference, 0.21; 95% CI, 0.01 to 0.41; P = .04). Among 122 lipid-rich lesions, 34 of 55 (61.8%) in the alirocumab arm and 27 of 67 (41.8%) in the placebo arm showed a less lipid-rich plaque phenotype at follow-up (P = .03). Among 63 lesions with thin-cap fibroatheroma at baseline, 8 of 26 (30.8%) in the alirocumab arm and 3 of 37 (8.1%) in the placebo arm showed a fibrous/fibrocalcific plaque phenotype at follow-up (P = .02).
Conclusions And Relevance:
At the lesion level, very intensive lipid-lowering therapy induced substantially greater PAV regression than described in previous vessel-level analyses. Compared with statin therapy alone, alirocumab treatment was associated with greater enlargement of the lesion MLA and more frequent transition of presumably high-risk plaque phenotypes into more stable, less lipid-rich plaque phenotypes.
Trial Registration:
ClinicalTrials.gov Identifier: NCT03067844.
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