Lesion-Level Effects of LDL-C-Lowering Therapy in Patients With Acute Myocardial Infarction: A Post Hoc Analysis of the PACMAN-AMI Trial.

Autor:	Biccirè FG; Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland., Kakizaki R; Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland., Koskinas KC; Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland., Ueki Y; Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland., Häner J; Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland., Shibutani H; Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland., Lønborg J; Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Spitzer E; Cardialysis, Rotterdam, the Netherlands.; Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands., Iglesias JF; Department of Cardiology, Geneva University Hospital, Geneva, Switzerland., Otsuka T; Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland., Siontis GCM; Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland., Stortecky S; Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland., Kaiser C; Department of Cardiology, Basel University Hospital, Basel, Switzerland., Ambühl M; Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland., Morf L; Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland., Ondracek AS; Department of Cardiology, Medical University of Vienna, Vienna, Austria., van Geuns RJ; Department of Cardiology, Radboud UMC, Nijmegen, the Netherlands., Spirk D; Institute of Pharmacology, Bern University Hospital, University of Bern, Bern, Switzerland, and Sanofi, Switzerland., Daemen J; Department of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands., Mach F; Department of Cardiology, Geneva University Hospital, Geneva, Switzerland., Windecker S; Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland., Engstrøm T; Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Lang I; Department of Cardiology, Medical University of Vienna, Vienna, Austria., Losdat S; CTU Bern, University of Bern, Bern, Switzerland., Räber L; Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland.
Jazyk:	angličtina
Zdroj:	JAMA cardiology [JAMA Cardiol] 2024 Sep 02. Date of Electronic Publication: 2024 Sep 02.
DOI:	10.1001/jamacardio.2024.3200
Abstrakt:	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.
Databáze:	MEDLINE
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