CARotid plaqUe StabilizatiOn and Regression With Evolocumab.
CARotid plaqUe StabilizatiOn and Regression With Evolocumab.
The CARUSO trial aims at investigating the efficacy of evolocumab in promoting carotid plaque
 morphological stabilization and regression as compared to traditional lipid lowering therapy
 (LLT). Primary end-point of the study is the superiority of evolocumab on top of ongoing LLT
 versus ongoing LLT in carotid plaque morphological stabilization and regression at 6 and 12
 months, respectively. Secondary end-points are: LDL-Cholesterol (LDL-C) absolute and
 percentage changes in the two groups at 12 month follow-up, and adverse cerebrovascular and
 cardiac events at 12 and 24 months
Optimal lipid-lowering therapy (LLT) is a mainstay for the therapeutic management of
 atherosclerotic vascular disease. Cardiac and cerebrovascular adverse events and progression
 of atherosclerosis are, indeed, reduced in proportion to the achieved LDL cholesterol (LDL-C)
 levels.In addition, regression of atherosclerotic plaques with optimal LLT has been observed.
 However, optimal LLT with statin and ezetimibe, might be limited by the onset of adverse
 effects (i.e. disabling myalgias, diarrhea) with are usually dose -dependent, and the maximum
 tolerated statin dose might be insufficient to reach the recommended LDL-C goals. The advent
 of proprotein convertase subtilisin kexin type 9 inhibitors (PCSK9i) has allowed the
 achievement of very low LDL-C levels, and the fulfillment of the recommended LDL-C targets.
 However, while the experience with PCSK9i in patients with coronary artery disease has been
 wide, and coronary plaque regression has been documented, little is known regarding carotid
 plaque regression following therapy with PCSK9i. Only a few case reports have been published,
 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.
Inclusion Criteria:

 asymptomatic patients with uni- or bilateral carotid artery stenosis ≥50% and LDL-C values
 ≥100 mg/dL despite ongoing lipid lowering therapy

 Exclusion Criteria:

 -  age <18 or ≥81 years old

 -  known intolerance to evolocumab

 -  ongoing or previous treatment with PCSK9i

 -  prior stroke or transient ischemic attack

 -  total carotid occlusion

 -  major active infection or major hematologic, renal, hepatic, or endocrine dysfunction

 -  malignancy with life expectancy below 24 months

 -  failure to sign informed consent