Can we reverse atherogenesis with the eradication of toxic LDL-C? A comparative pooled analysis of selected therapies in quest of the revolutionary approach

Abstract

Abstract Background The LDL-C is a toxic substrate of progressive atherosclerosis and the concept of the cumulative LDL-C exposure is proved in Mendelian trials. The eradication of LDL-C becomes a critical clinical target. Notwithstanding can we truly manage a related arterial remodeling that remains a question. Purpose The aim of the study was to estimate the atheroprotective disparities in the relevant lipid-lowering intravascular imaging studies in comparison with novel transient scaffolding and nanomedicine-based strategies. Methods This hypothesis-generating pooled subanalysis comparatively evaluates patterns of the regression of atherosclerosis in Caucasian and East Asian populations (EAP) in 38 intravascular ultrasound (IVUS) imaging studies (N=9,146). The analysis has revealed 7 so-called Classic (51.1% of the total analyzed population) studies (conducted by the group of Nicholls/ Nissen) with mostly Caucasian population, 18 clinical studies (31.7%) with White/ Caucasian population, and 13 trials (17.2%) with EAP (11 Japanese studies, 2 – South Korean, and 1 – Chinese). Results The regression of atherosclerosis was documented in 18 of 38 studies. A −1.67±5.99% mean absolute reduction of PB reported in all 38 studies with a −18.46±20.35% decrease of LDL cholesterol. The Glagovian threshold of a 40% plaque burden/ percent atheroma volume (PB) was achieved in one study, a NANOM-FIM trial (a 30.7% reduction of PB at 12 months, p<0.05, see a Figure). The invasive ABSORB A (a 1.63% PB increase at 24-month follow-up, p<0.02) and ABSORB B1 (a 2.46% PB decrease at 60-month follow-up, the p-value was about 0.06) studies revealed a progression of atherosclerosis after implantation of bioresorbable scaffolds. Only the ABSORB B2 study demonstrated that transient scaffolding has a potential to manage atherogenesis (a 1.1% PB decrease at 36 months, the p-value is about 0.05). A pooled linear regression analysis revealed a moderate association between LDL-C and PB (r=0.3314, p=0.008) with an LDL-C threshold of 106 mg/dl (a 80 mg/dl in Classic Caucasian randomized studies, a 88 mg/dl threshold – in the rest Caucasian studies, and a 123 mg/dl - in East Asian studies; R2=0.0953, r=0.3314, p=0.008 for pooled studies). The EAP studies substantially differ from Caucasian trials by the smaller size of both lesions and vessels. Unlike the modest 0.14±0.94% (p=0.89) progression of atherosclerosis in classic studies (p=0.11) LDL-C reduction), the EAP demonstrate a −1.99±3.57% (p=0.19) atheroregression amid a mean −31.29±15.66% (p<0.0001) decrease of LDL-C. Conclusion LDL-C threshold of 106 mg/dl is a target for any lipid-lowering strategy to accomplish the regression of atherosclerosis. The lower LDL-C level is associated with a better atheroprotective effect. The invasive strategies grant a promise to properly treat arterial remodeling. A comparative analysis Funding Acknowledgement Type of funding source: Private company. Main funding source(s): De Haar Research Task Force, Rotterdam, The Netherlands