P4606Comparing biomarker profiles in patients with stable atherosclerosis treated with anacetrapib versus placebo: a nested proteomic study from HPS3/TIMI 55-REVEAL

Abstract

Abstract Background The cholesteryl ester transfer protein (CETP) inhibitor anacetrapib improves cardiovascular outcomes in patients with stable atherosclerosis; however, the potential interaction of HDL-C-, LDL-C-, and non-lipid-mediated effects remains incompletely understood. Purpose The aim of this study was to identify biological pathways that are influenced by treatment with anacetrapib. Methods HPS3/TIMI 55-REVEAL was a randomized, double-blind, placebo-controlled trial of anacetrapib in patients with stable atherosclerotic cardiovascular disease. We performed a nested prospective biomarker study in 500 patients, analyzing 274 candidate biomarkers. We compared changes in biomarker levels between randomization and mid-study (∼2 years) in patients treated with anacetrapib vs. placebo using a stringent threshold for statistical significance. We evaluated associations between changes in selected biomarkers and changes in HDL-C and LDL-C from baseline to mid-study in each treatment group. Results Eleven biomarkers were significantly modified by anacetrapib vs. placebo (Figure). These proteins represent pathways implicated in inflammation, lipid metabolism, and hematopoiesis. Among anacetrapib-treated patients, changes in 5/11 biomarkers were not significantly correlated with changes in either serum HDL-C or serum LDL-C. Conclusion(s) In patients with stable atherosclerosis, treatment with anacetrapib results in changes in protein expression extending beyond lipid metabolism. Some of these changes appear to be independent of anacetrapib-mediated effects on HDL-C and LDL-C. Acknowledgement/Funding HPS3/TIMI 55-REVEAL was sponsored by Merck.