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. 2023 Oct 31;82(18):1737-1747.
doi: 10.1016/j.jacc.2023.08.019. Epub 2023 Aug 26.

Concomitant Coronary Atheroma Regression and Stabilization in Response to Lipid-Lowering Therapy

Flavio G Biccirè  1 , Jonas Häner  2 , Sylvain Losdat  3 , Yasushi Ueki  2 , Hiroki Shibutani  2 , Tatsuhiko Otsuka  2 , Ryota Kakizaki  2 , Thomas M Hofbauer  4 , Robert-Jan van Geuns  5 , Stefan Stortecky  2 , George C M Siontis  2 , Sarah Bär  2 , Jacob Lønborg  6 , Dik Heg  3 , Christoph Kaiser  7 , David Spirk  8 , Joost Daemen  9 , Juan F Iglesias  10 , Stephan Windecker  2 , Thomas Engstrøm  6 , Irene Lang  4 , Konstantinos C Koskinas  2 , Lorenz Räber  11
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Free article

Concomitant Coronary Atheroma Regression and Stabilization in Response to Lipid-Lowering Therapy

Flavio G Biccirè et al. J Am Coll Cardiol. .
Free article

Abstract

Background: The frequency, characteristics, and outcomes of patients treated with high-intensity lipid-lowering therapy and showing concomitant atheroma volume reduction, lipid content reduction, and increase in fibrous cap thickness (ie, triple regression) are unknown.

Objectives: This study was designed to investigate rates, determinants, and prognostic implications of triple regression in patients presenting with acute myocardial infarction and treated with high-intensity lipid-lowering therapy.

Methods: The PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients with Acute Myocardial Infarction) trial used serial intravascular ultrasound, near-infrared spectroscopy, and optical coherence tomography to compare the effects of alirocumab vs placebo in patients receiving high-intensity statin therapy. Triple regression was defined by the combined presence of percentage of atheroma volume reduction, maximum lipid core burden index within 4 mm reduction, and minimal fibrous cap thickness increase. Clinical outcomes at 1-year follow-up were assessed.

Results: Overall, 84 patients (31.7%) showed triple regression (40.8% in the alirocumab group vs 23.0% in the placebo group; P = 0.002). On-treatment low-density lipoprotein cholesterol levels were lower in patients with vs without triple regression (between-group difference: -27.1 mg/dL; 95% CI: -37.7 to -16.6 mg/dL; P < 0.001). Triple regression was independently predicted by alirocumab treatment (OR: 2.83; 95% CI: 1.57-5.16; P = 0.001) and a higher baseline maximum lipid core burden index within 4 mm (OR: 1.03; 95% CI: 1.01-1.06; P = 0.013). The composite clinical endpoint of death, myocardial infarction, and ischemia-driven revascularization occurred less frequently in patients with vs without triple regression (8.3% vs 18.2%; P = 0.04).

Conclusions: Triple regression occurred in one-third of patients with acute myocardial infarction who were receiving high-intensity lipid-lowering therapy and was associated with alirocumab treatment, higher baseline lipid content, and reduced cardiovascular events. (Vascular Effects of Alirocumab in Acute MI-Patients [PACMAN-AMI]; NCT03067844).

Keywords: acute coronary syndromes; atherosclerosis; intravascular ultrasound; lipid lowering; optical coherence tomography, PCSK9 inhibitors.

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Conflict of interest statement

Funding Support and Author Disclosures This study was conducted in an independent academic setting and funded by Bern University Hospital. Dr Ueki has received personal fees and nonfinancial support from NIPRO; and has received personal fees from Amgen, Daiichi-Sankyo, Abbott Vascular, Kowa, and Novartis, outside the submitted work. Dr Kakizaki has received speaker fees from Abbott Medical Japan, Philips Japan, Mochida Pharmaceutical Japan, Novartis Japan, Kowa Japan, Takeda Pharmaceuticals Japan, Ono Pharmaceutical Japan, Boehringer Ingelheim Japan, Daiichi-Sankyo Japan, Mitsubishi Tanabe Pharma Japan, and Eli Lilly Japan, outside the submitted work. Dr Hofbauer has received speaker fees from Sanofi. Dr Stortecky has received research grants paid to the institution from Edwards Lifesciences, Medtronic, Abbott Vascular, and Boston Scientific; and has received speaker fees from Boston Scientific. Dr Bär has received research grants paid to the institution from Medis Medical Imaging, Abbott, and Bangerter-Rhyner Stiftung, outside the submitted work; and has received a personal research grant from the Swiss National Science Foundation, outside the submitted work. Dr Spirk has received personal fees from Sanofi (Suisse), outside the submitted work. Dr Räber has received grants from Sanofi, Regeneron, and Infraredx paid to Inselspital; has received speaker fees from Sanofi during the conduct of the study; has received grants from Abbott, Heartflow, Boston Scientific, and Biotronik paid to Inselspital; and has received grants from Abbott, Amgen, AstraZeneca, Occlutech, Sanofi, Canon, and Medtronic for speaker and consultation fees outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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