Early and Short-term Use of PCSK9-Inhibitors on Coronary Plaque Stability in Acute Coronary Syndrome

Abstract Aims Proprotein convertase anti-subtilisin–kexin type 9 inhibitors (PCSK9Is) improve plaque volume and composition and reduce major adverse coronary events in chronic coronary artery disease. We evaluated the effects of the short-term use of PCSK9Is on coronary plaque stability in patients with acute coronary syndrome (ACS) using optical coherence tomography (OCT). Methods and results This is a multicentre, open-label randomized controlled trial. The enrolled 80 subjects met the inclusion criteria. Of these, 52 patients (age 60 ± 11 years, 38 men, 14 women) with ST-elevated ACS had undergone successful primary percutaneous coronary intervention with LDL-cholesterol (LDL-C) levels > 70 mg/dL while receiving high-intensity statins. Participants were randomly assigned to the PCSK9I group (evolocumab 420 mg for 3 months, n = 29) or the standard of care (SoC) group (n = 23). Optical coherence tomography was performed at baseline (BL) and 3 and 9 months after randomization to assess lipid-rich plaques in non-culprit lesions. The change in the minimum fibrous cap thickness (MFCT) from BL to 9 months was the primary endpoint. The percentage change in LDL-C levels from BL to 3 months was significantly greater in the PCSK9I group (−67.8 ± 21.5% in the PCSK9I group vs. −16.3 ± 21.8% in the SoC group; P < 0.0001), and the difference between the two groups disappeared from BL to 9 months (−20.0 ± 37.8% in the PCSK9I group vs. −6.7 ± 34.2% in the SoC group; P = 0.20). The changes in MFCT from BL to 9 months were significantly greater in the PCSK9I group, even after PCSK9I discontinuation {100 μm [interquartile range (IQR): 45–180 μm] vs. 50 μm [IQR: 0–110 μm]; P = 0.032}. Conclusion Combination treatment with PCSK9Is and statins resulted in more marked plaque stabilization after ACS than SoC alone, and this effect persisted for 6 months after PCSK9I discontinuation. Registration Adage-Joto study, UMIN ID No. 26516.