Reductions in VLDL and remnant cholesterol through inhibition of ANGPTL3 protein synthesis: An analysis from TRANSLATE-TIMI 70

Background and Aims : VLDL and remnant cholesterol are increasingly recognized risk factors for MI with few targeted therapeutic options. Vupanorsen is an antisense oligonucleotide that inhibits the synthesis of ANGPTL3, a regulator of cholesterol metabolism.Methods: TRANSLATE-TIMI 70 was a double-blind, randomized controlled trial testing 7 dose regimens of vupanorsen (SC Q4W: 80, 120, 160 mg; SC Q2W: 60, 80, 120, 160 mg) in adults with elevated triglycerides (150-500 mg/dl) and non-HDL-C ≥100 mg/dl on statin therapy. ANGPTL3, direct VLDL-C, and remnant cholesterol (calculated as total cholesterol - direct LDL-C - HDL-C) were assessed over 24 weeks.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Conclusions: Inhibition of ANGPTL3 protein synthesis significantly lowers VLDL and remnant cholesterol, with the magnitude of reduction directly related to degree of ANGPTL3 lowering. ANGPTL3 inhibition may have a role in patients with residual dyslipidemia despite LDL-lowering therapy. Background and Aims : VLDL and remnant cholesterol are increasingly recognized risk factors for MI with few targeted therapeutic options. Vupanorsen is an antisense oligonucleotide that inhibits the synthesis of ANGPTL3, a regulator of cholesterol metabolism. Methods: TRANSLATE-TIMI 70 was a double-blind, randomized controlled trial testing 7 dose regimens of vupanorsen (SC Q4W: 80, 120, 160 mg; SC Q2W: 60, 80, 120, 160 mg) in adults with elevated triglycerides (150-500 mg/dl) and non-HDL-C ≥100 mg/dl on statin therapy. ANGPTL3, direct VLDL-C, and remnant cholesterol (calculated as total cholesterol - direct LDL-C - HDL-C) were assessed over 24 weeks. Conclusions: Inhibition of ANGPTL3 protein synthesis significantly lowers VLDL and remnant cholesterol, with the magnitude of reduction directly related to degree of ANGPTL3 lowering. ANGPTL3 inhibition may have a role in patients with residual dyslipidemia despite LDL-lowering therapy.