The PACMAN-AMI trial: game over for the "vulnerable plaque"?

The PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction) trial is an investigator-initiated, multicentre, double-blind, randomized clinical trial aiming to determine the effects of 1-year treatment with the proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor alirocumab in addition to statin therapy on coronary atherosclerosis assessed by serial multimodality intracoronary imaging in patients with acute myocardial infarction (AMI).1 The primary hypothesis was that, when compared with placebo, treatment with alirocumab would determine a greater reduction in percent atheroma volume (PAV) in non-infarct-related arteries (IRAs), as measured by serial intravascular ultrasound (IVUS). At nine European centres, 300 patients (mostly statin-naive) with AMI undergoing percutaneous coronary intervention (PCI) of the IRA and successful multimodality intracoronary imaging of two non-IRAs were randomized to receive biweekly subcutaneous alirocumab 150 mg (n= 148) or placebo (n= 152), initiated,24 h after urgent PCI of the culprit lesion, and continued for 52 weeks in addition to rosuvastatin 20 mg, without dose adjustment in either treatment. Patients underwent multimodality invasive imaging with IVUS, near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT) in the proximal segments of two non-IRAs during the index procedure and after 52 weeks. The primary endpoint was the change in PAV assessed by IVUS. The two powered secondary endpoints were: (i) the change in the maximum lipid core burden index (LCBI) within 4 mm assessed by NIRS and (ii) the change in minimal fibrous cap thickness measured by OCT imaging. Out of 300 randomized patients (mean age, 59 years; 19% females), 265 (88%) underwent serial IVUS imaging in 537 arteries. At Week 52, the mean change in PAV was -2.13% with alirocumab vs. -0.92% with placebo [difference, -1.21; 95% confidence interval (CI), -1.78 to -0.65%; P, 0.001]. When compared with placebo, patients randomized to alirocumab showed a significantly greater reduction in maximum LCBI within 4 mm (difference, -41.24; 95% CI, -70.71 to -11.77; P= 0.006), and a significantly greater increase in minimal fibrous cap thickness (difference, 29.65 mu m; 95% CI, 11.75-47.55; P= 0.001). At Week 52, LDL cholesterol (LDL-C) level was 23.6+ 23.8 mg/dL in the alirocumab group and 74.4+ 30.5 mg/dL in the placebo group (P= 0.001), representing 85 and 51% reduction vs. baseline, respectively. Patients in the alirocumab group also showed significantly greater decreases in triglycerides, lipoprotein(a), and apolipoprotein B, without significant difference in high-sensitivity C-reactive protein levels.