Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study

Abstract

Bempedoic acid may provide an oral therapeutic option complementary to ezetimibe in statin intolerant patients who require additional LDL-C lowering.

Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy

“…In the monotherapy arms, LDL-cholesterol lowering was 30% with bempedoic acid 180 mg and 21% with ezetimibe 10 mg. 15 The addition of bempedoic acid 180 mg to stable ezetimibe therapy with or without other lipid-modifying therapies (including statins) in a phase 3 study yielded an additional 24% LDLcholesterol lowering. 9 Together, these results indicate a complementary effect on LDL-cholesterol lowering when combining bempedoic acid and ezetimibe. BA þ EZE FDC lowered LDL-cholesterol to a degree generally consistent across demographic and clinical subgroups, including patients receiving various intensities of background statin therapy.…”

“…6 In pivotal clinical trials, bempedoic acid as monotherapy or when added to background lipidlowering therapy significantly lowered LDL-cholesterol as well as other relevant lipids and biomarkers. [9][10][11][12] Therapeutic interventions whose lipid-lowering effects are attributed to the upregulation of LDL receptor expression (e.g. diet, statins, ezetimibe, bile acid sequestrants and ileal bypass surgery) have been shown to reduce adverse cardiovascular outcome risk commensurate with the magnitude of LDL-cholesterol reduction.…”

Targeting Foam Cell Formation in Atherosclerosis: Therapeutic Potential of Natural Products

“…Bempedoic Acid (ETC-1002). Bempedoic acid (ETC-1002), a small-molecule inhibitor of ATP citrate lyase, has been shown to reduce the level of low-density lipoprotein (LDL) cholesterol and the development of atherosclerosis in hypercholesterolemic ApoE 2/2 mice (Pinkosky et al, 2016), LDLR 2/2 mice (Samsoondar et al, 2017), LDLR-deficient miniature pigs (Samsoondar et al, 2017), and statin-intolerant hypercholesterolemic patients (Ballantyne et al, 2018;Laufs et al, 2019). Bempedoic acid, as a prodrug, is converted to the active agent in liver, but not in skeletal muscle; therefore, bempedoic acid may avoid myotoxicity associated with statin therapy (Penson et al, 2017;Ruscica et al, 2019).…”

Emerging Strategies for the Management of Atherogenic Dyslipidaemia

“…Bempedoic acid (ETC-1002) [16][17][18][19] Adenosine triphosphate citrate lyase inhibitor ↓LDL-C, non-HDL-C, ApoB, and hs-CRP Inclisiran (ALN-PCSSC) [20][21][22][23] PCSK9 siRNA ↓PCSK9, ApoB, LDL-C, non-HDL-C, VLDL-C AKCEA-APO(a)-LRx 14,24 ApoA antisense oligonucleotides ↓Lp(a) Volanesorsen (ISIS 304801, ISIS-ApoCIIIRx and IONIS-ApoCIIIRx) [25][26][27] ApoC3 antisense ↓TG, TC, ApoB, non-HDL-C, VLDL-C ↑HDL-C IONIS-ANGPTL3 28,29 ANGPTL3 antisense oligonucleotides ↓TG, VLDL-C, non-HDL-C, LDL-C, HDL-C Epanova 30,31 Omega-3 in free fatty acid form ↓ TG Evinacumab (REGN1500) [32][33][34] ANGPTL3 monoclonal antibody ↓TG, non-HDL-C, LDL-C, TC, and HDL-C ANGPTL3 = angiopoietin-like 3; ApoB = apolipoprotein B; HDL-C = HDL cholesterol; LDL-C = LDL cholesterol; PCSK9 = proprotein convertase subtilisin/kexin type 9; siRNA = small interfering RNA; TC = total cholesterol; TG = triglycerides; VLDL-C = very LDL cholesterol.…”