Morphological stabilization and regression of carotid plaque following therapy with evolocumab in a high‐risk patient

Abstract

Lipid‐lowering therapy is a mainstay for the management of coronary and carotid disease. Actually, progression of atherosclerosis and adverse events are reduced in proportion to the achieved levels of LDL cholesterol (LDL‐C). A 67‐year‐old patient underwent two hospitalizations 6 months apart due to acute coronary syndromes. In the first, PCI with drug‐eluting stents (DES) was performed to treat ulcerated stenoses in the left anterior descending artery. In the second, lipid‐rich critical disease was found on the right coronary artery and treated with PCI + DES. Later, carotid duplex ultra‐sonography (DU) was done due to some episodes of dizziness. It showed an 80% critical stenosis (peak systolic velocity, PSV 239 cm/s) of the left internal carotid artery (LICA) with high‐risk features (hypoechogenic and irregular plaque with “fluffy” components). In consideration of the plaque morphology and the unmet LDL‐C targets, evolocumab was added to the ongoing statin therapy. In the following months, we observed a parallel trend between carotid plaque regression and LDL‐C lowering. Initial plaque remodeling was seen after 5 months: the atheroma appeared fibrotic, with no more fluffy components. At 10 months, in conjunction with the achievement of LDL‐C goal (23 mg/dl), a fibrocalcific atheroma was observed; PSV, after an initial rise, fell to 229 cm/s. No further cardiovascular event occurred at 46 months. Last DUS showed a 60% fibrocalcific mid LICA stenosis with PSV of 180 cm/s. Our experience highlights the important role of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors in promoting remodeling and hopefully regression of atherosclerotic plaques.

CARotid plaqUe StabilizatiOn and regression with evolocumab: Rationale and design of the CARUSO study

“…These changes have been associated with increased plaque stability 32 . Carotid plaque stabilization, in fact, progressively continued in conjunction with the achievement of very low LDL‐C levels, and at 10 months carotid plaque regression was seen also 10 . Accordingly, we settled up 6 and 12 months as the ideal follow‐up time period to observe both morphological stabilization and carotid plaque regression (Table 3).…”

“…32 Carotid plaque stabilization, in fact, progressively continued in conjunction with the achievement of very low LDL-C levels, and at 10 months carotid plaque regression was seen also. 10 Accordingly, we settled up 6 and 12 months as the ideal follow-up time period to observe both morphological stabilization and carotid plaque regression (Table 3). This is in line with evidence from statin 33 and PCSK9i 9,34 trials, which indicate that the full clinical benefits of LDL-lowering may emerge after about 1 year from LLT optimization.…”

“…Previous experiences (Table 1) with PCSK9i promoting remodeling and regression of carotid plaques are limited to case reports, but they have consistently shown a parallel trend between LDL‐C lowering and morphological stabilization and regression of the carotid plaque 10 . In particular, initial morphological stabilization of a high‐risk carotid plaque (hypoechogenic, soft, irregular and lipid‐rich plaque with ''fluffy'' components) was seen 5 months after the implementation of LLT with the addition of evolocumab; fibrotic remodeling of the atheroma occurred, and fluffy components were not detected anymore.…”

“…7 While the experience with PCSK9i in patients with coronary artery disease has been wide, 3,8,9 and coronary plaque regression has been documented, 5 little is known regarding carotid plaque regression following therapy with PCSK9i. Only a few case reports have been published (Table 1), 10 and no observational study has been carried out so far. Furthermore, morphological carotid plaque stabilization has a prognostic role, and the possibility of its early achievement with PCSK9i may be relevant especially in the context of percutaneous or surgical carotid interventions.…”

Carotid Atherosclerosis, Ultrasound and Lipoproteins

“…Therefore, the inhibition of PCSK9 with monoclonal antibodies leads to increased expression and recycling of LDL-R on the cell surface, resulting in rapid clearance of LDL-C and a 50–60% reduction in cholesterolemia [ 62 ]. The addition of PCSK9 inhibitors to existing lipid-lowering therapy, and the achievement of very low levels of cholesterol, has brought about, in some case reports, morphological stabilization and regression of carotid plaques [ 63 , 64 ]. Overall, we can affirm that the presence of carotid plaques with a low echogenicity is an important prognostic factor in predicting future cerebrovascular and cardiovascular events, with an association between the carotid plaques and the plasma concentration of some lipid levels, particularly cholesterol contained in triglyceride-rich lipoproteins.…”