CARotid plaqUe StabilizatiOn and regression with evolocumab: Rationale and design of the CARUSO study.
carotid artery disease
drugs/pharmacotherapy
imaging
lipids
Journal
Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions
ISSN: 1522-726X
Titre abrégé: Catheter Cardiovasc Interv
Pays: United States
ID NLM: 100884139
Informations de publication
Date de publication:
01 07 2021
01 07 2021
Historique:
revised:
06
04
2021
received:
21
03
2021
accepted:
16
04
2021
pubmed:
25
4
2021
medline:
21
10
2021
entrez:
24
4
2021
Statut:
ppublish
Résumé
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 the role of these drugs on carotid plaque regression. The CARotid plaqUe StabilizatiOn and regression with evolocumab (CARUSO) study is a randomized, single-center, investigator-initiated trial aiming at evaluating carotid plaque morphological stabilization and regression following, respectively, 6 and 12 months of therapy with evolocumab. Asymptomatic patients with uni- or bilateral de novo carotid artery stenosis ≥50% and LDL-C values ≥100 mg/dl despite maximum tolerated lipid lowering therapy (LLT) will be randomized to evolocumab 140 mg s.c. every 2 weeks on top of ongoing LLT, or no additional treatment. 100 patients (50 in each arm) will be enrolled. Serial carotid duplex ultra-sonography will be performed to monitor the carotid plaque morphology and stenosis over time. The primary end point of the study is, (a) carotid plaque morphological stabilization at 6 months, defined as defined as the disappearance of ulcerations and fluffy components and the achievement of a regular plaque morphology with prevalence of fibrous atheroma and/or (b) carotid plaque regression at 12 months, defined as reduction of the entity of the stenosis and/or peak systolic velocity by at least 5%, as compared with baseline. The CARUSO trial will test the superiority of evolocumab on top of ongoing LLT versus ongoing LLT alone regarding carotid plaque morphological stabilization and regression. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Sections du résumé
BACKGROUND
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 the role of these drugs on carotid plaque regression. The CARotid plaqUe StabilizatiOn and regression with evolocumab (CARUSO) study is a randomized, single-center, investigator-initiated trial aiming at evaluating carotid plaque morphological stabilization and regression following, respectively, 6 and 12 months of therapy with evolocumab.
METHODS
Asymptomatic patients with uni- or bilateral de novo carotid artery stenosis ≥50% and LDL-C values ≥100 mg/dl despite maximum tolerated lipid lowering therapy (LLT) will be randomized to evolocumab 140 mg s.c. every 2 weeks on top of ongoing LLT, or no additional treatment. 100 patients (50 in each arm) will be enrolled. Serial carotid duplex ultra-sonography will be performed to monitor the carotid plaque morphology and stenosis over time.
RESULTS
The primary end point of the study is, (a) carotid plaque morphological stabilization at 6 months, defined as defined as the disappearance of ulcerations and fluffy components and the achievement of a regular plaque morphology with prevalence of fibrous atheroma and/or (b) carotid plaque regression at 12 months, defined as reduction of the entity of the stenosis and/or peak systolic velocity by at least 5%, as compared with baseline.
CONCLUSION
The CARUSO trial will test the superiority of evolocumab on top of ongoing LLT versus ongoing LLT alone regarding carotid plaque morphological stabilization and regression. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Substances chimiques
Antibodies, Monoclonal, Humanized
0
evolocumab
LKC0U3A8NJ
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
E115-E121Informations de copyright
© 2021 Wiley Periodicals LLC.
Références
Cholesterol Treatment Trialists C, Fulcher J, O'Connell R, et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet. 2015;385(9976):1397-1405.
Giugliano RP, Mach F, Zavitz K, et al. Cognitive function in a randomized trial of evolocumab. N Engl J Med. 2017;377(7):633-643.
Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(22):2097-2107.
Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387-2397.
Nicholls SJ, Puri R, Anderson T, et al. Effect of evolocumab on progression of coronary disease in statin-treated patients: the GLAGOV randomized clinical trial. JAMA. 2016;316(22):2373-2384.
Tsujita K, Sugiyama S, Sumida H, et al. Impact of dual lipid-lowering strategy with ezetimibe and atorvastatin on coronary plaque regression in patients with percutaneous coronary intervention: the multicenter randomized controlled PRECISE-IVUS trial. J Am Coll Cardiol. 2015;66(5):495-507.
Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111-188.
Guedeney P, Giustino G, Sorrentino S, et al. Efficacy and safety of alirocumab and evolocumab: a systematic review and meta-analysis of randomized controlled trials. Eur Heart J. 2019. https://doi.org/10.1093/eurheartj/ehz430. [Epub ahead of print].
Sabatine MS, Giugliano RP, Keech AC, et al. And others. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713-1722.
Aranzulla TC, Musumeci G. Morphological stabilization and regression of carotid plaque following therapy with evolocumab in a high-risk patient. Catheter Cardiovasc Interv. 2021;97(6):E835-E841.
Grant EG, Benson CB, Moneta GL, et al. And others. Carotid artery stenosis: gray-scale and Doppler US diagnosis-Society of Radiologists in ultrasound consensus conference. Radiology. 2003;229(2):340-346.
Sprynger M, Rigo F, Moonen M, et al. Focus on echovascular imaging assessment of arterial disease: complement to the ESC guidelines (PARTIM 1) in collaboration with the working group on aorta and peripheral vascular diseases. Eur Heart J Cardiovasc Imaging. 2018;19(11):1195-1221.
Staikov IN, Arnold M, Mattle HP, et al. Comparison of the ECST, CC, and NASCET grading methods and ultrasound for assessing carotid stenosis. European carotid surgery trial. North American symptomatic carotid endarterectomy trial. J Neurol. 2000;247(9):681-686.
Kelly AG, Holloway RG. Review: noninvasive imaging techniques may be useful for diagnosing 70% to 99% carotid stenosis in symptomatic patients. ACP J Club. 2006;145(3):77.
Huibers A, de Borst GJ, Wan S, et al. Non-invasive carotid artery imaging to identify the vulnerable plaque: current status and future goals. Eur J Vasc Endovasc Surg. 2015;50(5):563-572.
Saba L, Sanfilippo R, Sannia S, et al. Association between carotid artery plaque volume, composition, and ulceration: a retrospective assessment with MDCT. AJR Am J Roentgenol. 2012;199(1):151-156.
Ahmadi A, Argulian E, Leipsic J, Newby DE, Narula J. From subclinical atherosclerosis to plaque progression and acute coronary events: JACC state-of-the-art review. J Am Coll Cardiol. 2019;74(12):1608-1617.
Giannopoulos A, Kakkos S, Abbott A, et al. Long-term mortality in patients with asymptomatic carotid stenosis: implications for statin therapy. Eur J Vasc Endovasc Surg. 2015;50(5):573-582.
McDermott MM, Mandapat AL, Moates A, et al. Knowledge and attitudes regarding cardiovascular disease risk and prevention in patients with coronary or peripheral arterial disease. Arch Intern Med. 2003;163(18):2157-2162.
Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the Management of Blood Cholesterol: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Circulation. 2019;139(25):e1082-e1143.
Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1500-1509.
McGirt MJ, Perler BA, Brooke BS, et al. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors reduce the risk of perioperative stroke and mortality after carotid endarterectomy. J Vasc Surg. 2005;42(5):829-836.
Yamada K, Yoshimura S, Kawasaki M, et al. Effects of atorvastatin on carotid atherosclerotic plaques: a randomized trial for quantitative tissue characterization of carotid atherosclerotic plaques with integrated backscatter ultrasound. Cerebrovasc Dis. 2009;28(4):417-424.
Sabatine MS. PCSK9 inhibitors: clinical evidence and implementation. Nat Rev Cardiol. 2019;16(3):155-165.
O'Donoghue ML, Fazio S, Giugliano RP, et al. Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk. Circulation. 2019;139(12):1483-1492.
Xie W, Liu J, Wang W, et al. Association between plasma PCSK9 levels and 10-year progression of carotid atherosclerosis beyond LDL-C: a cohort study. Int J Cardiol. 2016;215:293-298.
Lee CJ, Lee YH, Park SW, et al. Association of serum proprotein convertase subtilisin/kexin type 9 with carotid intima media thickness in hypertensive subjects. Metabolism. 2013;62(6):845-850.
Cheng JM, Oemrawsingh RM, Garcia-Garcia HM, et al. PCSK9 in relation to coronary plaque inflammation: results of the ATHEROREMO-IVUS study. Atherosclerosis. 2016;248:117-122.
Bohula EA, Giugliano RP, Leiter LA, et al. Inflammatory and Cholesterol risk in the FOURIER trial. Circulation. 2018;138(2):131-140.
Schuster S, Rubil S, Endres M, et al. Anti-PCSK9 antibodies inhibit pro-atherogenic mechanisms in APOE*3Leiden.CETP mice. Sci Rep. 2019;9(1):11079.
Hirai K, Imamura S, Hirai A, Ookawara S, Morishita Y. Effects of evolocumab on carotid intima-media thickness and clinical parameters in patients taking a statin. J Clin Med. 2020;9:2256.
Libby P. How does lipid lowering prevent coronary events? New insights from human imaging trials. Eur Heart J. 2015;36(8):472-474.
Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267-1278.
Ference BA, Cannon CP, Landmesser U, Luscher TF, Catapano AL, Ray KK. Reduction of low density lipoprotein-cholesterol and cardiovascular events with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors and statins: an analysis of FOURIER, SPIRE, and the Cholesterol Treatment Trialists collaboration. Eur Heart J. 2018;39(27):2540-2545.
Giugliano RP, Pedersen TR, Park JG, et al. Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial. Lancet. 2017;390(10106):1962-1971.
Seng NSHL, Kyaw H, Min Tun N, et al. Significant regression of carotid artery stenosis after treatment with proprotein convertase subtilisin/kexin type 9 serine protease inhibitor. Urol Nephrol Open Access J. 2019;7(5):92-94.
Ogata A, Oho K, Matsumoto N, et al. Stabilization of vulnerable carotid plaques with proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab. Acta Neurochir. 2019;161(3):597-600.
Wilson A. 2017. My journey with familial hypercholesterolemia and heart disease.
US National Library of Medicine.Assessment of Atherosclerotic Plaque Characteristics Change by DCE-MRI With Alirocumab.
US National Library of Medicine.PCSK9 Inhibition in Patients With Symptomatic Intracranial Atherosclerosis (PINNACLE).
US National Library of Medicine.Effect of Evolocumab on Carotid Plaque Composition in Asymptomatic Carotid Artery Stenosis (EVOCAR-1).