Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial

• Published in: JAMA : the journal of the American Medical Association 2022-05, Vol.327 (18), p.1771-1781
• Main Authors: Räber, Lorenz, Ueki, Yasushi, Otsuka, Tatsuhiko, Losdat, Sylvain, Häner, Jonas D, Lonborg, Jacob, Fahrni, Gregor, Iglesias, Juan F, van Geuns, Robert-Jan, Ondracek, Anna S, Radu Juul Jensen, Maria D, Zanchin, Christian, Stortecky, Stefan, Spirk, David, Siontis, George C. M, Saleh, Lanja, Matter, Christian M, Daemen, Joost, Mach, François, Heg, Dik, Windecker, Stephan, Engstrøm, Thomas, Lang, Irene M, Koskinas, Konstantinos C
• Format: Article
• Language: English
• Subjects: Aged; Angioplasty; Antibodies, Monoclonal, Humanized - therapeutic use; Arteries; Arteriosclerosis; Atherosclerosis; Cholesterol; Cholesterol, LDL; Clinical trials; Comments; Coronary artery; Coronary Artery Disease - complications; Coronary Artery Disease - diagnostic imaging; Coronary Artery Disease - drug therapy; Double-Blind Method; Female; Heart attacks; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; I.R. radiation; Infrared spectra; Infrared spectroscopy; Kexin; Lipids; Male; Medical imaging; Middle Aged; Monoclonal antibodies; Myocardial infarction; Myocardial Infarction - complications; Myocardial Infarction - drug therapy; Near infrared radiation; Online First; Optical Coherence Tomography; Original Investigation; Patients; PCSK9 Inhibitors - therapeutic use; Placebos; Plaque, Atherosclerotic - complications; Plaque, Atherosclerotic - diagnostic imaging; Plaque, Atherosclerotic - drug therapy; Plaques; Proprotein convertases; Spectrum analysis; Statins; Subtilisin; Therapy; Thickness; Tomography; Treatment Outcome
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.2022.5218

IMPORTANCE: Coronary plaques that are prone to rupture and cause adverse cardiac events are characterized by large plaque burden, large lipid content, and thin fibrous caps. Statins can halt the progression of coronary atherosclerosis; however, the effect of the proprotein convertase subtilisin kexin type 9 inhibitor alirocumab added to statin therapy on plaque burden and composition remains largely unknown. OBJECTIVE: To determine the effects of alirocumab on coronary atherosclerosis using serial multimodality intracoronary imaging in patients with acute myocardial infarction. DESIGN, SETTING, AND PARTICIPANTS: The PACMAN-AMI double-blind, placebo-controlled, randomized clinical trial (enrollment: May 9, 2017, through October 7, 2020; final follow-up: October 13, 2021) enrolled 300 patients undergoing percutaneous coronary intervention for acute myocardial infarction at 9 academic European hospitals. INTERVENTIONS: Patients were randomized to receive biweekly subcutaneous alirocumab (150 mg; n = 148) or placebo (n = 152), initiated less than 24 hours after urgent percutaneous coronary intervention of the culprit lesion, for 52 weeks in addition to high-intensity statin therapy (rosuvastatin, 20 mg). MAIN OUTCOMES AND MEASURES: Intravascular ultrasonography (IVUS), near-infrared spectroscopy, and optical coherence tomography were serially performed in the 2 non–infarct-related coronary arteries at baseline and after 52 weeks. The primary efficacy end point was the change in IVUS-derived percent atheroma volume from baseline to week 52. Two powered secondary end points were changes in near-infrared spectroscopy–derived maximum lipid core burden index within 4 mm (higher values indicating greater lipid content) and optical coherence tomography–derived minimal fibrous cap thickness (smaller values indicating thin-capped, vulnerable plaques) from baseline to week 52. RESULTS: Among 300 randomized patients (mean [SD] age, 58.5 [9.7] years; 56 [18.7%] women; mean [SD] low-density lipoprotein cholesterol level, 152.4 [33.8] mg/dL), 265 (88.3%) underwent serial IVUS imaging in 537 arteries. At 52 weeks, mean change in percent atheroma volume was −2.13% with alirocumab vs −0.92% with placebo (difference, −1.21% [95% CI, −1.78% to −0.65%], P