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

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). This multicenter, open label randomized controlled trial. Enrolled 80 subjects met the inclusion criteria. Of these, 52 patients (age 60±11 years, 38 men, 14 women) with ST-elevated ACS who had undergone successful primary percutaneous coronary intervention with low-density lipoprotein cholesterol (LDL-C) levels >70 mg/dL while receiving high-intensity statins. Participants were randomly assigned to the PCSK9Is group (evolocumab 420 mg for 3 months, N=29) or the standard of care (SoC) group(N=23). OCT was performed at baseline (BL) and 3-months (3M) and 9- months (9M) after randomization to assess lipid-rich plaques in non-culprit lesions.The change in the minimum fibrous cap thickness (MFCT) from baseline to 9M was the primary endpoint. The percentage change in LDL-C levels from BL to 3M were significantly greater in the PCSK9Is group (-67.8±21.5% in the PCSK9Is group vs. -16.3±21.8% in the SoC group; p<0.0001) and though, the difference between two groups were disappeared from BL to 9M (-20.0±37.8% in the PCSK9Is group vs. -6.7±34.2% in the SoC group; p=0.20).The changes in MFCT from baseline to 9M were significantly greater in the PCSK9Is group, even after PCSK9Is discontinuation (100 μm [Interquartile range (IQR): 45–180 μm] vs. 50 μm [IQR: 0–110 μm]; p=0.032). 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. Adage-Joto study, UMIN ID No. 26516