Lipid lowering with bempedoic acid added to a proprotein convertase subtilisin/kexin type 9 inhibitor therapy: A randomized, controlled trial

Abstract

•Bempedoic acid added to PCSK9 inhibitor therapy lowered LDL-C by 30.3% vs placebo.•Bempedoic acid significantly lowered Apo B, non-HDL-C, total cholesterol, and hsCRP.•The safety profile of bempedoic acid in combination with a PCSK9i was generally comparable to placebo. BackgroundProprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) lower low-density lipoprotein cholesterol (LDL-C) in patients with hypercholesterolemia. However, some patients receiving PCSK9i therapy might require additional lipid-lowering therapy (LLT) to reach LDL-C goals. Bempedoic acid is an oral, once-daily, ATP-citrate lyase inhibitor that significantly lowers LDL-C in patients with hypercholesterolemia when given alone or as add-on therapy to statins and/or ezetimibe.ObjectiveAssess safety and efficacy of bempedoic acid added to PCSK9i (evolocumab) background therapy in patients with hypercholesterolemia.MethodsThis phase 2, randomized, double-blind, placebo-controlled study was conducted in three phases: 1.5-month screening/washout period including discontinuation of all LLTs, a 3-month period wherein patients initiated background PCSK9i therapy, and a 2-month treatment period in which patients were randomized 1:1 to receive bempedoic acid 180 mg or placebo once daily while continuing PCSK9i therapy.ResultsOf 59 patients randomized, 57 completed the study. Mean baseline LDL-C after 3 months of PCSK9i background therapy was 103.1 ± ± 30.4 mg/dL. Bempedoic acid added to background PCSK9i therapy significantly lowered LDL-C by 30.3% (P < .001) vs placebo. Compared with placebo, bempedoic acid significantly lowered apolipoprotein B, non–high-density lipoprotein cholesterol, and total cholesterol (nominal P < .001 for all), and high-sensitivity C-reactive protein (P = .029). When added to background PCSK9i therapy, the safety profile of bempedoic acid was comparable to that observed for placebo.ConclusionsWhen added to a background of PCSK9i therapy, bempedoic acid significantly lowered LDL-C levels with a safety profile comparable to placebo in patients with hypercholesterolemia. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) lower low-density lipoprotein cholesterol (LDL-C) in patients with hypercholesterolemia. However, some patients receiving PCSK9i therapy might require additional lipid-lowering therapy (LLT) to reach LDL-C goals. Bempedoic acid is an oral, once-daily, ATP-citrate lyase inhibitor that significantly lowers LDL-C in patients with hypercholesterolemia when given alone or as add-on therapy to statins and/or ezetimibe. Assess safety and efficacy of bempedoic acid added to PCSK9i (evolocumab) background therapy in patients with hypercholesterolemia. This phase 2, randomized, double-blind, placebo-controlled study was conducted in three phases: 1.5-month screening/washout period including discontinuation of all LLTs, a 3-month period wherein patients initiated background PCSK9i therapy, and a 2-month treatment period in which patients were randomized 1:1 to receive bempedoic acid 180 mg or placebo once daily while continuing PCSK9i therapy. Of 59 patients randomized, 57 completed the study. Mean baseline LDL-C after 3 months of PCSK9i background therapy was 103.1 ± ± 30.4 mg/dL. Bempedoic acid added to background PCSK9i therapy significantly lowered LDL-C by 30.3% (P < .001) vs placebo. Compared with placebo, bempedoic acid significantly lowered apolipoprotein B, non–high-density lipoprotein cholesterol, and total cholesterol (nominal P < .001 for all), and high-sensitivity C-reactive protein (P = .029). When added to background PCSK9i therapy, the safety profile of bempedoic acid was comparable to that observed for placebo. When added to a background of PCSK9i therapy, bempedoic acid significantly lowered LDL-C levels with a safety profile comparable to placebo in patients with hypercholesterolemia.

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