Physicians' Academy for Cardiovascular Education

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


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.”


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