Angiographic stenosis regression with PCSK9 inhibitor in acute MI

Impact of alirocumab on plaque regression and haemodynamics of non-culprit arteries in patients with acute myocardial infarction: a prespecified substudy of the PACMAN-AMI trial

Literature - Bär S, Kavaliauskaite R, Otsuka T, et al. - EuroIntervention. 2023 Jul 17;19(4):e286-e296. doi: 10.4244/EIJ-D-23-00201

Introduction and methods


Several intracoronary imaging RCTs, including the PACMAN-AMI trial, have shown that treatment with PCSK9 inhibitors on top of statins induces plaque regression and stabilization [1-3]. However, whether these effects also lead to improvement of coronary physiology and changes in angiographic diameter stenosis remains unknown.

Aim of the study

In a prespecified substudy of the PACMAN-AMI trial, the authors assessed the effects of the PCSK9 inhibitor alirocumab, when added to high-intensity statin therapy, on the quantitative flow ratio (QFR) and percent diameter stenosis in non-obstructive coronary lesions located in non–infarct-related arteries at 1 year after acute MI (AMI).


The PACMAN-AMI (Effects of the PCSK9 Antibody AliroCuMab on Coronary Atherosclerosis in PatieNts with Acute Myocardial Infarction. A Serial, Multivessel, Intravascular Ultrasound, Near-Infrared Spectroscopy And Optical Coherence Tomography Imaging Study) trial was a multicenter, investigator-initiated, double-blind, placebo-controlled RCT conducted at 9 academic centers in Switzerland, Austria, Denmark, and the Netherlands [4]. In this trial, 300 AMI patients undergoing PCI were randomized to subcutaneous alirocumab 150 mg biweekly or placebo, in addition to high-intensity statin therapy with rosuvastatin 20 mg. All participants underwent serial coronary angiography and intravascular imaging at baseline and 1-year follow-up. Diameter stenosis was assessed by 3D quantitative coronary angiography (QCA).

In the current substudy, 193 patients with any non–infarct-related artery ≥2.0 mm and percent diameter stenosis 26%–49% were included (282 non–infarct-related arteries in total).


The prespecified primary endpoint was the number of patients with a mean QFR increase across non–infarct-related arteries between baseline and 1 year. Secondary endpoints included the continuous change in percent diameter stenosis by 3D-QCA.

Main results

  • At baseline, median QFR was 0.96 (IQR: 0.91–0.98) in patients treated with alirocumab and 0.96 (IQR: 0.91–0.99) in placebo-treated patients (P=0.593).
  • The number of patients with a mean QFR increase across non–infarct-related arteries from baseline to 1 year (primary endpoint) was 50 of 94 patients (53.2%; 95%CI: 43.2%–63.0%) in the alirocumab group compared with 40 of 99 patients (40.4%; 95%CI: 31.3%–50.3%) in the placebo group (difference: 12.8%; 95%CI: −2.2% to 27.8%; OR: 1.7; 95%CI: 0.9–3.0; P=0.076).
  • A sensitivity analysis among non–infarct-related arteries with QFR ≤0.95 did show a significantly higher number of patients with a mean QFR increase on alirocumab (n=37/57; 64.9%; 95%CI: 51.9%–76.0%) versus placebo (n=22/50; 44.0%; 95%CI: 31.2%–7.7%) (difference: 20.9%; 95%CI: 0.5%–41.0% ; OR: 2.4; 95%CI: 1.1–5.2; P=0.031).
  • At baseline, there was also no difference in mean ± SD percent diameter stenosis between the alirocumab and placebo arms (36.96 ± 7.88% vs. 36.63 ± 8.46%; P=0.742).
  • After 1 year, mean ± SD change in percent diameter stenosis (secondary endpoint) was –1.03 ± 7.28% in the alirocumab group versus 1.70 ± 8.27% in the placebo group (difference: –2.50%; 95%CI: –4.43% to –0.57%; P=0.011). This difference was more pronounced in the sensitivity analysis considering only non–infarct-related arteries with QFR ≤0.95 (alirocumab: –1.53 ± 7.63% vs. placebo: 2.74 ± 9.67%; difference: –4.11%; 95%CI: –7.41% to –0.80%; P=0.015).
  • Exploratory analyses of data from the PACMAN-AMI trial and 6 statin trials that assessed percent diameter stenosis by 2D-QCA indicated an association between the change in percent diameter stenosis and on-treatment LDL-c levels (beta: 0.013; P<0.001).
  • There was a trend towards a more pronounced reduction in percent diameter stenosis with alirocumab versus placebo with a higher degree of baseline stenosis (up to –3.98% for baseline percent diameter stenosis >45%).


In AMI patients undergoing PCI, intensive lipid-lowering therapy with alirocumab for 1 year, in addition to high-intensity statin therapy, resulted in a 1.0% regression of the angiographic percent diameter stenosis of non-obstructive coronary lesions, compared with a 1.7% increase with placebo. However, there was no significant difference in coronary physiology between the treatment groups (as indicated by the number of patients with a mean QFR increase across non–infarct-related arteries). Exclusion of vessels with the least flow limitation (i.e., QFR >0.95) suggested “alirocumab may exert a small but significant beneficial effect on coronary hemodynamics in more flow-limiting disease.”


1. Räber L, Ueki Y, Otsuka T, Losdat S, Häner JD, Lonborg J, Fahrni G, Iglesias JF, van Geuns RJ, Ondracek AS, Radu Juul Jensen MD, Zanchin C, Stortecky S, Spirk D, Siontis GCM, Saleh L, Matter CM, Daemen J, Mach F, Heg D, Windecker S, Engstrøm T, Lang IM, Koskinas KC; PACMAN-AMI collaborators. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial. JAMA. 2022;327:1771-81.

2. Nicholls SJ, Puri R, Anderson T, Ballantyne CM, Cho L, Kastelein JJP, Koenig W, Somaratne R, Kassahun H, Yang J, Wasserman SM, Scott R, Ungi I, Podolec J, Ophuis AO, Cornel JH, Borgman M, Brennan DM, Nissen SE. Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial. JAMA. 2016;316:2373-84.

3. Nicholls SJ, Kataoka Y, Nissen SE, Prati F, Windecker S, Puri R, Hucko T, Aradi D, Herrman JR, Hermanides RS, Wang B, Wang H, Butters J, Di Giovanni G, Jones S, Pompili G, Psaltis PJ. Effect of Evolocumab on Coronary Plaque Phenotype and Burden in Statin-Treated Patients Following Myocardial Infarction. JACC Cardiovasc Imaging. 2022;15:1308-21.

4. Zanchin C, Koskinas KC, Ueki Y, Losdat S, Häner JD, Bär S, Otsuka T, Inderkum A, Jensen MRJ, Lonborg J, Fahrni G, Ondracek AS, Daemen J, van Geuns RJ, Iglesias JF, Matter CM, Spirk D, Juni P, Mach F, Heg D, Engstrom T, Lang I, Windecker S, Räber L. Effects of the PCSK9 antibody alirocumab on coronary atherosclerosis in patients with acute myocardial infarction: a serial, multivessel, intravascular ultrasound, near-infrared spectroscopy and optical coherence tomography imaging study–Rationale and design of the PACMAN-AMI trial. Am Heart J. 2021;238:33-44.

Find this article online at EuroIntervention.

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