Atherosclerosis, Vascular Biology and Development
Session Title: HDL and the Artery Wall
Abstract 20280: Impact of the Cholesteryl Ester Transfer Protein Inhibitor Evacetrapib on Cholesterol Efflux Capacity in High Risk Patients Within the ACCELERATE Trial
Abstract
Background: The cholesteryl ester transfer protein (CETP) inhibitor, evacetrapib (Eva), did not reduce cardiovascular events in the ACCELERATE trial when added to high intensity statin despite favorable plasma lipid changes. The effects of evacetrapib on HDL function (as measured by cholesterol efflux capacity, or CEC) in this trial are of interest and could help understand the outcome.
Methods: Global, ABCA1 and non-ABCA1 dependent HDL CEC were determined in 283 high-risk vascular Participants who were all treated with high intensity statin and randomized to either evacetrapib or placebo in ACCELERATE. The impact of diabetes and recent acute coronary syndrome (ACS) event on CEC changes with evacetrapib was also investigated.
Results: Evacetrapib produced substantial increases in HDL-C (+133 v +2%, P<0.0001), apoA-I (+51 v +1%, P<0.0001) and apoC-III (+51 v +6%, P<0.0001) compared with placebo. Consistent with the increased HDL-C, evacetrapib produced significant increases in global (+41.6 v +6.2%, P<0.0001) and non-ABCA1 dependent (+62.6 v +0.7%, P<0.0001) CEC compared with placebo. However, evacetrapib did not significantly increase ABCA1 dependent CEC (+27.0 v +8.4%, P=0.64). Changes in global and non-ABCA1 dependent CEC directly correlated with changes in HDL-C, apoA-I and apoC-III and inversely correlated with changes in high-sensitivity C-reactive protein (hs-CRP). Evacetrapib produced effects on HDL CEC in patients with and without diabetes and in patients at different lengths of time from an index ACS event (Table).
Conclusions: In the ACCELERATE trial, evacetrapib added to high intensity statin increased global and non-ABCA1 dependent but not ABCA1 dependent HDL CEC. The potential implications of increases in inflammatory markers to the lack of clinical benefit of evacetrapib require further investigation.
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