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 trialLiterature - 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 . 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.
- 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.”