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World J Cardiol. Sep 26, 2021; 13(9): 472-482
Published online Sep 26, 2021. doi: 10.4330/wjc.v13.i9.472
Intensive lipid-lowering therapy, time to think beyond low-density lipoprotein cholesterol
Ahmed Abdalwahab, Ayman Al-atta, Azfar Zaman, Mohammad Alkhalil
Ahmed Abdalwahab, Ayman Al-atta, Azfar Zaman, Mohammad Alkhalil, Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne NE7 7DN, United Kingdom
Ahmed Abdalwahab, Department of Cardiovascular Medicine, Faculty of Medicine, Tanta University, Tanta 35127, Egypt
Azfar Zaman, Mohammad Alkhalil, Vascular Biology, Newcastle University, Newcastle upon Tyne NE7 7DN, United Kingdom
Author contributions: Alkhalil M contributed to the conceptualization, methodology and project administration; Zaman A and Alkhalil M provided the resources; Abdalwahab A and Al-atta A contributed to writing original draft and preparation; all authors finally wrote review and edited the manuscript.
Conflict-of-interest statement: The authors have no any conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mohammad Alkhalil, DPhil, MRCP, Doctor, Cardiothoracic Centre, Freeman Hospital, Freeman Road, Newcastle upon Tyne NE7 7DN, United Kingdom. mak-83@hotmail.com
Received: March 21, 2021
Peer-review started: March 21, 2021
First decision: May 13, 2021
Revised: May 25, 2021
Accepted: July 21, 2021
Article in press: July 21, 2021
Published online: September 26, 2021
Processing time: 179 Days and 8.9 Hours
Abstract

Statins have been shown to be effective in reducing cardiovascular events. Their magnitude of benefits has been proportionate to the reduction in low-density lipoprotein cholesterol (LDL-c). Intensive lipid-lowering therapies using ezetimibe and more recently proprotein convertase subtilisin kexin 9 inhibitors have further improved clinical outcomes. Unselective application of these treatments is undesirable and unaffordable and, therefore, has been guided by LDL-c level. Nonetheless, the residual risk in the post-statin era is markedly heterogeneous, including thrombosis and inflammation risks. Moreover, the lipo-protein related risk is increasingly recognised to be related to other non-LDL-c markers such as Lp(a). Emerging data show that intensive lipid-lowering therapy produce larger absolute risk reduction in patients with polyvascular disease, post coronary artery bypass graft and diabetes. Notably, these clinical entities share similar phenotype of large burden of atherosclerotic plaques. Novel plaque imaging may aid decision making by identifying patients with propensity to develop lipid rich plagues at multi-vascular sites. Those patients may be suitable candidates for intensive lipid lowering treatment.

Keywords: Intensive lipid-lowering; Proprotein convertase subtilisin kexin 9 inhibitors; Ezetimibe; Plaque imaging; Low-density lipoprotein cholesterol

Core Tip: Intensive lipid-lowering therapies using ezetimibe and more recently proprotein convertase subtilisin kexin 9 inhibitors have improved clinical outcomes. Unselective application of these treatments is undesirable and unaffordable and, therefore, has been guided by low-density lipoprotein cholesterol level. Nonetheless, the residual risk in the post-statin era is markedly heterogeneous. Emerging data show that intensive lipid-lowering therapy produce larger absolute risk reduction in patients with polyvascular disease, post coronary artery bypass graft and diabetes. Notably, these clinical entities share similar phenotype of large burden of atherosclerotic plaques. Novel plaque imaging may aid decision making by identifying patients with propensity to develop lipid rich plagues at multi-vascular sites. Those patients may be suitable candidates for intensive lipid lowering treatment.