Intensive lipid-lowering therapy, time to think beyond low-density lipoprotein cholesterol

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.