Abstract 134: Atorvastatin As Opposed To Ezetimibe Reduces Biomarkers Of Thrombosis In The Setting Of Aggressive Lipid Lowering Therapy: Findings From The American Heart Association Strategically Focused Cardiometabolic Health And Type 2 Diabetes Mellitus Research Network

Abstract

Introduction: CHORD (CHOlesterol lowering and Residual Risk in Diabetes) is an ongoing, prospective, multicenter study designed to evaluate the effect of maximal cholesterol-lowering on cardiovascular (CV) risk. Aggressive lipid-lowering with HMG CoA-reductase inhibitors (e.g. statins), ezetimibe, and PCSK9 inhibitors (such as evolocumab) reduce atherothrombotic events. Statins reduce cholesterol dramatically and are also felt to have pleiotropic, anti-inflammatory properties. We compared the impact of statins and ezetimibe on thrombotic biomarkers after maximal lipid lowering with PCSK9 inhibition. Methods: CHORD enrolled subjects (n=57, mean age 52 ± 15 years, 44% male, 58% diabetes) with LDL-cholesterol >100mg/dl and treated with evolocumab (140mg every 2 weeks) plus either atorvastatin (80mg/day, n=27), or ezetimibe (10mg/day, n=30) for 30-days. High-sensitivity C-reactive protein (hs-CRP) and biomarkers of thrombosis (LEGENDplex Human Thrombosis Panel) were measured at baseline and follow-up. Results: Significant LDL-C reductions were observed in both the evolocumab + atorvastatin (130 mg/dl [123 - 145] to 31 mg/dl [27 - 39], p<0.001) and evolocumab + ezetimibe (127 mg/dl [106 - 138] to 38 mg/dl [27 - 56], p<0.001) groups. Hs-CRP was reduced after evolocumab + atorvastatin (18% reduction, p<0.01), but not evolocumab + ezetimibe. When compared to evolocumab + ezetimibe, greater reductions in P-selectin, D-Dimer, Factor IX, and a trend towards reduction in sCD40L, and PAI-1 were noted after evolocumab + atorvastatin ( Figure 1). Conclusion: Despite similar levels of LDL-C reduction, statins plus evolocumab cause greater reductions in biomarkers of thrombosis and inflammation than ezetimibe and evolocumab. These data suggest that statins provide benefits over and above LDL-C reduction.