PCSK9 and Coronary Artery Plaque-New Opportunity or Red Herring?

Abstract

Purpose of review: Although the clinical benefit of reducing low-density lipoprotein cholesterol (LDLc) in patients with coronary artery disease (CAD) is well-established, the impact on plaque composition and stability is less clear. Our narrative review aimed to assess the clinical effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on coronary plaque characteristics specifically focusing from atheroma progression to regression and stabilization.

Recent findings: The combination of statin therapy and PCSK9 inhibitors (evolocumab and alirocumab) promotes plaque stability in patients following an acute coronary syndrome. The GLAGOV study highlighted the relationship between achieved LDLc levels and changes in percentage atheroma volume. Similarly, the PACMAN-AMI study concluded that the qualitative and quantitative changes in coronary plaque were associated with the levels of LDLc. Assessing the severity of coronary artery stenosis and the extent of atherosclerotic burden by means of imaging techniques (e.g., IVUS, OCT and near-infrared spectroscopic) have significantly advanced our understanding of the benefits from promoting plaque regression and achieving to features of plaque stabilization through increasingly intensive lipid-lowering strategies.

Keywords: IVUS; Near-infrared spectroscopic; OCT; PCSK9 inhibitors; Plaque composition.

Fig. 1

Schematic representation of the effect of PCSK9 inhibition on plaque composition. CCTA, computed tomography coronary angiography; IVUS, intravascular ultrasound; NIRS, near-infrared spectroscopic imaging; OCT, optical coherence tomography; PCSK9, proprotein convertase subtilisin/kexin type 9