Adding alirocumab to rosuvastatin reduces coronary plaque in patients with acute MI

Adding alirocumab to rosuvastatin led to a significantly reduced coronary plaque in noninfarct-related arteries in patients with acute myocardial infarction (MI), according to the PACMAN-AMI* trial presented at ACC 2022.

This double-blind, placebo-controlled trial involved 300 patients (mean age 58.5 years, 18.7 percent female) with acute STEMI or non-STEMI who underwent percutaneous coronary intervention (PCI) at nine academic European hospitals. Participants were randomized to receive either subcutaneous alirocumab 150 mg twice a week (n=148) or placebo (n=152), initiated within 24 hours after PCI, in addition to rosuvastatin 20 mg daily. Coronary plaque characteristics were assessed by using serial, two-vessel, multimodality intracoronary imaging, such as intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT) for PAV**, LCBI***, and FCT⁺, respectively, at baseline and week 52. [ACC 2022, abstract 405-10]

At week 52, patients treated with alirocumab + rosuvastatin achieved a significantly greater reduction in mean PAV from baseline compared with placebo + rosuvastatin (-2.1 percent vs -0.9 percent; p=0.001).

Alirocumab + rosuvastatin recipients also achieved a significantly greater reduction in maximum LCBI at 4 mm (-79.4 vs -37.6 units; p=0.006) and mean angular extension of macrophages (-26.0 vs -16.0 degrees; p<0.001) from baseline to week 52 compared with placebo + rosuvastatin recipients.

Patients treated with alirocumab + rosuvastatin also demonstrated a significant increase in minimal FCT from baseline than those treated with placebo + rosuvastatin at week 52 (62.7 vs 33.2 µm; p=0.001)

Adverse events (AEs) did not differ between the alirocumab + rosuvastatin and placebo + rosuvastatin arms (71.0 percent vs 73.0 percent [any AEs] and 32.0 percent vs 33.0 percent [serious AEs]), except for general allergic reactions that occurred in 3.4 percent of patients in the alirocumab arm compared with none in the placebo arm.

AEs led to study drug discontinuation in a slightly higher proportion of patients in the alirocumab arm than the placebo arm (1.4 percent vs 0.0 percent).

There was no difference in the rate of prespecified clinical events between the alirocumab and placebo arms, specifically all-cause death (1.4 percent vs 0.7 percent; p=0.55) or MI (1.4 percent vs 2.0 percent; p=0.24).

“Alirocumab, initiated in the setting of acute AMI on top of high-intensity statin therapy [ie, rosuvastatin,] resulted in a greater decrease in PAV, larger reduction in lipid burden, and higher increase in minimal FCT after 52 weeks of treatment,” said lead author Professor Lorenz Räber from the Department of Cardiology at Bern University Hospital in Bern, Switzerland.

“These findings indicate incremental coronary plaque regression, lipid core reduction, and plaque stabilization with alirocumab and provide a mechanistic rationale in favour of early initiation of very intensive LDL-C⁺⁺ lowering in acute MI patients,” he added.

*PACMAN-AMI: Vascular effects of alirocumab in acute MI-patients

**PAV: Percent atheroma volume

***LCBI: Lipid-core burden index

⁺FCT: Fibrous cap thickness

⁺⁺LDL-C: Low-density lipoprotein cholesterol