Alirocumab initiation after MI associated with lower plasma atheroma volume: PACMAN-AMI

By Wally A. Omar, MD on

Key Points

  • PCSK-9 inhibitors have emerged as a viable treatment option patients hypercholesterolemia despite adequate tolerance of statin therapies.
  • The role of thin capped fibrous atheromas with a lipid rich pool in causing myocardial infarction is well described, but the effect of PCSK-9 inhibitors on these plaques is yet to be explored
  • PACMAN-AMI randomized patients presenting with acute myocardial infarction to receive alirocumab, a PCSK-9 inhibitor, or placebo in addition to high intensity statin. At baseline and 52 weeks, coronary imaging was performed with the use of intravascular ultrasound and optical coherence tomography to assess changes in plaque burden.
  • At 52 weeks, there was a substantial improvement in overall plaque volume, and thickening of fibrous atheroma caps, suggesting alirocumab confers protection from myocardial infarction.

It has been well-established that many presentations of acute coronary syndrome are caused by plaque rupture from thin-capped fibrous atheromas with a lipid-rich core. While PCSK-9 inhibitors have been shown to effectively decrease low-density lipoproteins (LDL) in patients already taking statins, their effect on coronary plaque physiology have been less studied. In a late breaking clinical trial session at the 71st annual American College of Cardiology Scientific Sessions, Dr. Lorenz Raber presented the findings of the PACMAN-AMI study, which sought to investigate the effect of alirocumab on coronary plaque when initiated after patients present with acute coronary syndrome.

In this randomized control trial, patents presenting with acute coronary syndrome undergoing coronary angiography were enrolled if they had successful PCI of the culprit vessel and 2 non-infarct arteries with evidence of atherosclerosis. These patients then underwent intracoronary imaging using intravascular ultrasound, near-infrared spectroscopy, or optical coherence tomography. Blood sampling was also performed at baseline. Participants were then randomized to receive alirocumab or placebo in addition to their high intensity statin. At 52 weeks, patients presented again for intracoronary imaging assessment as well as follow-up blood testing.

The primary endpoint was a change in the percent atheroma volume by IVUS and secondary endpoints were maximal lipid-core burden index and minimal fibrous cap thickness by NIRS and OCT respectively. In this multinational European study, 148 patients were randomized to the treatment arm and 152 to the placebo arm. Almost half of the patients presented with STEMI.

At 52 weeks, there was a significant difference in the change in LDL-C with alirocumab versus placebo. All endpoints were significant with alirocumab as well. For the primary endpoint, alirocumab conferred a greater change in percent atheroma volume (-2.1 vs. -0.9[-1.8 to 10.7], p =0.0001). Furthermore, on OCT imaging, there was a 62.7 µm increased in fibrous cap thickness in the alirocumab group compared to 33.2 µm in placebo. There were no significant differences in the adverse event and safety endpoints either.

The authors concluded that alirocumab resulted in a greater decrease in plasma atheroma volume, decrease in lipid burden and increase in minimal fibrous cap thickness after 52 weeks of treatment. This adds to the knowledge that statins can stabilize coronary plaque, and promote early initiation of LDL-C lowering medications after acute myocardial infarction.

The findings were simultaneously published in JAMA.