Coronary Plaque Regression: A Review of the Role of Lipid-Lowering Agents

Anish Adhikari; Caleb Wutawunashe; Michael Kim; Arber Kodra

doi:10.1055/a-2692-1482

International Journal of Angiology, Table of Contents

Int J Angiol 2025; 34(04): 272-275
DOI: 10.1055/a-2692-1482

Review Article

Coronary Plaque Regression: A Review of the Role of Lipid-Lowering Agents

Authors

Anish Adhikari

¹Department of Interventional Cardiology, Lenox Hill Hospital, Northwell Health, New York, New York
Caleb Wutawunashe

¹Department of Interventional Cardiology, Lenox Hill Hospital, Northwell Health, New York, New York
Michael Kim

¹Department of Interventional Cardiology, Lenox Hill Hospital, Northwell Health, New York, New York
Arber Kodra

¹Department of Interventional Cardiology, Lenox Hill Hospital, Northwell Health, New York, New York

Abstract

The burden of coronary artery disease (CAD) globally is substantial. Lipid-lowering therapies (LLT) significantly reduce the morbidity and mortality associated with CAD. The advent of more sophisticated imaging modalities of the coronary arteries, including intravascular ultrasound, optical coherence tomography, and coronary computed tomography angiography with calcium scoring, has allowed for evaluation of changes in plaque composition and volume as surrogates of plaque regression. LLTs, particularly statins and proprotein convertase subtilisin/kexin type 9 inhibitors, are effective in reducing low-density lipoprotein cholesterol and reducing cardiovascular mortality. This review synthesizes the evidence on the efficacy of various LLT agents in promoting plaque regression.

Keywords

lipid - plaque regression - IVUS - OCT - statins - cardiovascular disease - cardiovascular risk factors

Full Text

References

References
1 Stary HC, Chandler AB, Dinsmore RE. et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation 1995; 92 (05) 1355-1374
2 Sabatine MS, Giugliano RP, Keech AC. et al; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017; 376 (18) 1713-1722
3 Mihaylova B, Emberson J, Blackwell L. et al; Cholesterol Treatment Trialists' (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 2012; 380 (9841): 581-590
4 Cannon CP, Blazing MA, Giugliano RP. et al; IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372 (25) 2387-2397
5 Schwartz GG, Steg PG, Szarek M. et al; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med 2018; 379 (22) 2097-2107
6 Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 1995; 92 (03) 657-671
7 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
8 Li J, Montarello NJ, Hoogendoorn A. et al. Multimodality intravascular imaging of high-risk coronary plaque. JACC Cardiovasc Imaging 2022; 15 (01) 145-159
9 Iatan I, Guan M, Humphries KH, Yeoh E, Mancini GBJ. Atherosclerotic coronary plaque regression and risk of adverse cardiovascular events: a systematic review and updated meta-regression analysis. JAMA Cardiol 2023; 8 (10) 937-945
10 Jang IK, Bouma BE, Kang DH. et al. Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound. J Am Coll Cardiol 2002; 39 (04) 604-609
11 Shaw LJ, Blankstein R, Bax JJ. et al. Society of Cardiovascular Computed Tomography/North American Society of Cardiovascular Imaging - expert consensus document on coronary CT imaging of atherosclerotic plaque. J Cardiovasc Comput Tomogr 2021; 15 (02) 93-109
12 Nissen SE, Tuzcu EM, Schoenhagen P. et al; REVERSAL Investigators. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA 2004; 291 (09) 1071-1080
13 Nicholls SJ, Ballantyne CM, Barter PJ. et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med 2011; 365 (22) 2078-2087
14 Hiro T, Kimura T, Morimoto T. et al; JAPAN-ACS Investigators. Effect of intensive statin therapy on regression of coronary atherosclerosis in patients with acute coronary syndrome: a multicenter randomized trial evaluated by volumetric intravascular ultrasound using pitavastatin versus atorvastatin (JAPAN-ACS [Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome] study). J Am Coll Cardiol 2009; 54 (04) 293-302
15 Dohi T, Miyauchi K, Okazaki S. et al. Early intensive statin treatment for six months improves long-term clinical outcomes in patients with acute coronary syndrome (Extended-ESTABLISH trial): a follow-up study. Atherosclerosis 2010; 210 (02) 497-502
16 Kawasaki M, Sano K, Okubo M. et al. Volumetric quantitative analysis of tissue characteristics of coronary plaques after statin therapy using three-dimensional integrated backscatter intravascular ultrasound. J Am Coll Cardiol 2005; 45 (12) 1946-1953
17 Nissen SE, Nicholls SJ, Sipahi I. et al; ASTEROID Investigators. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA 2006; 295 (13) 1556-1565
18 Takayama T, Hiro T, Yamagishi M. et al; COSMOS Investigators. Effect of rosuvastatin on coronary atheroma in stable coronary artery disease: multicenter coronary atherosclerosis study measuring effects of rosuvastatin using intravascular ultrasound in Japanese subjects (COSMOS). Circ J 2009; 73 (11) 2110-2117
19 Räber L, Taniwaki M, Zaugg S. et al; IBIS 4 (Integrated Biomarkers and Imaging Study-4) Trial Investigators (NCT00962416). Effect of high-intensity statin therapy on atherosclerosis in non-infarct-related coronary arteries (IBIS-4): a serial intravascular ultrasonography study. Eur Heart J 2015; 36 (08) 490-500
20 Kovarnik T, Chen Z, Mintz GS. et al. Plaque volume and plaque risk profile in diabetic vs. non-diabetic patients undergoing lipid-lowering therapy: a study based on 3D intravascular ultrasound and virtual histology. Cardiovasc Diabetol 2017; 16 (01) 156
21 Masuda J, Tanigawa T, Yamada T. et al. Effect of combination therapy of ezetimibe and rosuvastatin on regression of coronary atherosclerosis in patients with coronary artery disease. Int Heart J 2015; 56 (03) 278-285
22 Tsujita K, Sugiyama S, Sumida H. et al; PRECISE–IVUS Investigators. 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 (05) 495-507
23 Hougaard M, Hansen HS, Thayssen P. et al. Influence of ezetimibe in addition to high-dose atorvastatin therapy on plaque composition in patients with ST-segment elevation myocardial infarction assessed by serial: Intravascular ultrasound with iMap: the OCTIVUS trial. Cardiovasc Revasc Med 2017; 18 (02) 110-117
24 Hibi K, Sonoda S, Kawasaki M. et al; Ezetimibe-ACS Investigators. Effects of ezetimibe-statin combination therapy on coronary atherosclerosis in acute coronary syndrome. Circ J 2018; 82 (03) 757-766
25 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
26 Ako J, Hibi K, Tsujita K. et al. Effect of alirocumab on coronary atheroma volume in Japanese patients with acute coronary syndrome- the ODYSSEY J-IVUS trial. Circ J 2019; 83 (10) 2025-2033
27 Nishiguchi T, Kubo T, Tanimoto T. et al. Effect of early pitavastatin therapy on coronary fibrous-cap thickness assessed by optical coherence tomography in patients with acute coronary syndrome: the ESCORT study. JACC Cardiovasc Imaging 2018; 11 (06) 829-838
28 Komukai K, Kubo T, Kitabata H. et al. Effect of atorvastatin therapy on fibrous cap thickness in coronary atherosclerotic plaque as assessed by optical coherence tomography: the EASY-FIT study. J Am Coll Cardiol 2014; 64 (21) 2207-2217
29 Lo J, Lu MT, Ihenachor EJ. et al. Effects of statin therapy on coronary artery plaque volume and high-risk plaque morphology in HIV-infected patients with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial. Lancet HIV 2015; 2 (02) e52-e63
30 Zeb I, Li D, Nasir K. et al. Effect of statin treatment on coronary plaque progression - a serial coronary CT angiography study. Atherosclerosis 2013; 231 (02) 198-204
31 Inoue K, Motoyama S, Sarai M. et al. Serial coronary CT angiography-verified changes in plaque characteristics as an end point: evaluation of effect of statin intervention. JACC Cardiovasc Imaging 2010; 3 (07) 691-698
32 Yokoyama M, Komiyama N, Courtney BK. et al. Plasma low-density lipoprotein reduction and structural effects on coronary atherosclerotic plaques by atorvastatin as clinically assessed with intravascular ultrasound radio-frequency signal analysis: a randomized prospective study. Am Heart J 2005; 150 (02) 287
33 Lee SE, Chang HJ, Rizvi A. et al. Rationale and design of the progression of atherosclerotic plaque determined by computed tomographic angiography imaging (PARADIGM) registry: a comprehensive exploration of plaque progression and its impact on clinical outcomes from a multicenter serial coronary computed tomographic angiography study. Am Heart J 2016; 182: 72-79