Effect of evolocumab therapy on coronary fibrous cap thickness assessed by optical coherence tomography in patients with acute coronary syndrome

Abstract

Background: The addition of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, evolocumab, to statin therapy produced incremental regression of atherosclerotic plaques and a collaborative prevention of cardiovascular events in patients with coronary artery disease. The effect on fibrous-cup thickness, or extension of the atherosclerotic plaque with PCSK9-inhibitor, for several weeks after onset of acute coronary syndrome (ACS) has never been reported. Methods: This study aimed to examine the effect of evolocumab on fibrous-cap thickness, as well as the extent of the atherosclerotic plaque, by serial optical coherence tomography (OCT) analysis in patients with ACS. All patients received rosuvastatin 5 mg/day from at least 24 h after onset of ACS. Patients received evolocumab (140 mg every 2 weeks) 1 week after the onset of ACS in the statin plus evolocumab group. Patients took only rosuvastatin in the statin monotherapy group. OCT was performed to assess intermediate, non-culprit lesions just 4 and 12 weeks after emergent percutaneous coronary intervention. Results: OCT analysis revealed that the increase in fibrous-cap thickness and decrease in macrophage grade were greater with a narrower lipid arc and shorter lipid length, which were associated with lower low-density lipoprotein cholesterol (LDL-C) in the statin plus evolocumab group than in the statin alone treatments, even for a short term after ACS onset. Conclusions: Addition of the PCSK9-inhibitor evolocumab to statin therapy might produce incremental growth in fibrous-cap thickness and regression of the lipid-rich plaque, which were associated with greater reduction of LDL-C even for a short term in the early phase of ACS.

Association between apolipoprotein B/A1 ratio and coronary plaque vulnerability in patients with atherosclerotic cardiovascular disease: an intravascular optical coherence tomography study

“…Patients with low level of LDL-C who were treated with statins had a higher prevalence of calcification, which means that statins may help to prevent plaque rupture by calcification [ 45 ]. However, the addition of proprotein convertase subtilisin/kexin type 9 inhibitor to statin therapy might produce incremental growth in FCT and regression of the lipid-rich plaque after onset of ACS, thus decreasing the incidence of plaque rupture [ 46 ].…”

Effect of Alirocumab on Coronary Plaque in Patients With Coronary Artery Disease Assessed by Optical Coherence Tomography

“…OCT imaging analysis, which provides a detailed image of ten times greater resolution than that achieved with IVUS, is the ideal imaging modality to assess the fibrous cap thickness of coronary plaque [16,22]. In a recent retrospective, observational OCT study revealed that compared to statin monotherapy, statin plus evolocumab provided a greater increase in fibrous-cap thickness of coronary plaques in patients with recent acute coronary syndrome [23]. The results of our study were consistent with the previous findings and we demonstrated a significant greater increase in minimum lumen area in the alirocumab arm assessed by OCT imaging.…”

PCSK9 Functions in Atherosclerosis Are Not Limited to Plasmatic LDL-Cholesterol Regulation

“…In humans, PCSK9 inhibitors therapy added to statin therapy is capable of increasing fibrous cap thickening in acute coronary syndrome patients, reducing plaque vulnerability (82). However, the LDL-cholesterol lowering capacities of both PCSK9 inhibitors and statin treatment cannot solely explain the increased fibrous cap thickness suggesting that an unknown pleiotropic effect such as an anti-inflammatory effect independent of lowering LDLcholesterol may be involved (82).…”

“…In humans, PCSK9 inhibitors therapy added to statin therapy is capable of increasing fibrous cap thickening in acute coronary syndrome patients, reducing plaque vulnerability (82). However, the LDL-cholesterol lowering capacities of both PCSK9 inhibitors and statin treatment cannot solely explain the increased fibrous cap thickness suggesting that an unknown pleiotropic effect such as an anti-inflammatory effect independent of lowering LDLcholesterol may be involved (82). PCSK9 inhibitor treatment in an atherogenic mouse model increased the number of circulating endothelial progenitor cells and circulating angiogenic cells, markers of endothelial and vascular health associated with positive outcomes as reduced occurrence of cardiovascular events and death associated to cardiovascular causes (83).…”