Lesion-Level Effects of LDL-C–Lowering Therapy in Patients With Acute Myocardial Infarction
Authors: Flavio G. Biccirè, Ryota Kakizaki, Konstantinos C. Koskinas, Yasushi Ueki, Jonas Häner, Hiroki Shibutani, Jacob Lønborg, Ernest Spitzer, Juan F. Iglesias, Tatsuhiko Otsuka, George C. M. Siontis, Stefan Stortecky, Christoph Kaiser, Maria Ambühl, Laura Morf, Anna S. Ondracek, Robert-Jan van Geuns, David Spirk, Joost Daemen, François Mach, Stephan Windecker, Thomas Engstrøm, Irene Lang, Sylvain Losdat, Lorenz Räber
Journal: JAMA Cardiology (2024)

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 &amp;amp;lt; .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 &amp;amp;lt; .001). MLA increased by 0.15 mm 2 with alirocumab and decreased by 0.07 mm 2 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