Patients with a history of acute myocardial infarction (AMI) remain at elevated risk for recurrent ischemic cardiovascular events despite early initiation of statins. The ODYSSEY OUTCOMES trial previously demonstrated that alirocumab, a proprotein convertase subtilisin-kexin type 9 inhibitor (PCSK9i), reduces risk of recurrent events when added to high intensity statin therapy.¹ The GLAGOV and HUYGENS trials investigated the impact of PCSK9i treatment with evolocumab in patients with stable coronary artery disease and found favorable changes to plaque characteristics.^2,3 Alterations in these characteristics with early PCSK9i treatment after AMI are of particular interest since high-risk lesions are often associated with non-infarct-related arteries (IRA).

PACMAN-AMI is a randomized, placebo-controlled, double-blinded clinical trial that enrolled 300 patients who underwent successful percutaneous coronary intervention (PCI) for AMI to start biweekly subcutaneous alirocumab or placebo within 24 hours of their PCI in addition to high-intensity statin.⁴ The primary endpoint demonstrated a greater reduction in mean percent atheroma volume (PAV) assessed by intravascular ultrasound (IVUS) after 52 weeks of alirocumab therapy (-2.13% vs. -0.92% in alirocumab vs. placebo, p < 0.001). Secondary endpoints demonstrated a reduction in the lipid core burden index assessed by near-infrared spectroscopy (NIRS) and a greater increase in minimal fibrous cap thickness assessed by optical coherence tomography (OCT) in the alirocumab arm. Adverse events were similar between groups.

Serial invasive imaging techniques in this study allowed for characterization of coronary plaque composition, phenotype, and evolution in multiple non-IRAs. The LDL-C levels achieved on PCSK9i treatment were well below current guideline thresholds (mean LDL-C 23.6 mg/dL in the alirocumab group compared with 74.4 mg/dL in the placebo group, mean change in LDL-C from baseline -131.2 vs. -76.5 mg/dL, p < 0.001) and translated to a greater reduction in IVUS-derived PAV. PACMAN-AMI provides evidence that an early, aggressive combination lipid lowering strategy with PCSK9i treatment on a background of statin therapy for high-risk patients may be beneficial. These results provide further mechanistic insights that suggest the degree of LDL-C lowering may lead to favorable coronary plaque changes. However, the effect of plaque volume reduction and changes in plaque characteristics on clinical outcomes has not yet been demonstrated, so further research is needed to validate these findings.

References

1. Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med 2018;379:2097-2107.
2. Nicholls SJ, Nissen SE, Prati F, et al. Assessing the impact of PCSK9 inhibition on coronary plaque phenotype with optical coherence tomography: rationale and design of the randomized, placebo-controlled HUYGENS study. Cardiovasc Diagn Ther 2021;11:120-29.
3. Nicholls SJ, Puri R, Anderson T, et al. Effect of evolocumab on progression of coronary disease in statin-treated patients: the GLAGOV randomized clinical trial. JAMA 2016;316:2373-84.
4. Räber L, Ueki Y, Otsuka T, et al. Effect of alirocumab added to high-intensity statin therapy on coronary atherosclerosis in patients with acute myocardial infarction: the PACMAN-AMI randomized clinical trial. JAMA 2022;327:1771-81.

Clinical Topics: Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and Coronary Artery Disease, Interventions and Imaging, Echocardiography/Ultrasound

Keywords: Primary Prevention, Secondary Prevention, ACC Annual Scientific Session, ACC22, Cholesterol, LDL, Antibodies, Monoclonal, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Plaque, Atherosclerotic, Coronary Artery Disease, Percutaneous Coronary Intervention, Tomography, Optical Coherence, Spectroscopy, Near-Infrared, Proprotein Convertases, Myocardial Infarction, Ultrasonography, Interventional, Subtilisins, Arteries, Phenotype

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