Alirocumab addition to statins significantly regresses plaque in non infarct-related coronary arteries

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. Therefore, Dr Lorenz Räber and his team conducted a study to determine the effects of alirocumab on coronary atherosclerosis using serial multimodality intracoronary imaging in patients with acute myocardial infarction.

The PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction) was a double-blind, placebo-controlled, randomized trial in which the researchers included 300 patients undergoing percutaneous coronary intervention for acute myocardial infarction. All patients received a high daily dose of the statin drug rosuvastatin (20 mg) and were randomized to receive biweekly subcutaneous alirocumab (150 mg; n = 148) or placebo (n = 152) for 2 weeks. The first injection was administered less than 24 hours after the insertion of a stent while patients were still in the hospital for their heart attacks.

Post stenting procedure, patients underwent three types of imaging in two other arteries of the heart. They were:

• Intravascular ultrasonography (IVUS),
• Near-infrared spectroscopy, and
• Optical coherence tomography.

At 52 weeks, the three imaging tests were repeated and the researchers analyzed the differences between before and after-treatment images. The major outcome assessed was the change in IVUS-derived per cent atheroma volume from baseline to week 52. Two powered secondary endpoints assessed 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.

Key findings of the study:

• At 52 weeks, the researchers found that the mean change in per cent atheroma volume was −2.13% with alirocumab vs −0.92% with placebo (difference, −1.21%).
• They noted that the mean change in maximum lipid core burden index within 4 mm was −79.42 with alirocumab vs −37.60 with placebo (difference, −41.24).
• They observed that the mean change in minimal fibrous cap thickness was 62.67 μm with alirocumab vs 33.19 μm with placebo (difference, 29.65 μm).
• They reported that the adverse events occurred in 70.7% of patients treated with alirocumab vs 72.8% of patients receiving a placebo.

The authors concluded, "Among patients with acute myocardial infarction, the addition of subcutaneous biweekly alirocumab, compared with placebo, to high-intensity statin therapy resulted in significantly greater coronary plaque regression in non–infarct-related arteries after 52 weeks. Further research is needed to understand whether alirocumab improves clinical outcomes in this population."

For further information:

DOI:10.1001/jama.2022.5218