Combination of bempedoic acid, ezetimibe, and atorvastatin in patients with hypercholesterolemia: A randomized clinical trial

• Published in: Atherosclerosis Vol. 320; pp. 122 - 128
• Main Authors: Rubino, John, MacDougall, Diane E., Sterling, Lulu R., Hanselman, Jeffrey C., Nicholls, Stephen J.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.03.2021
• Subjects: Bempedoic acid; Ezetimibe; Hypercholesterolemia; Lipid-lowering therapy; Low-density lipoprotein cholesterol; Statin; Hypercholesterolemia; Statin; Lipid-lowering therapy; Bempedoic acid; Low-density lipoprotein cholesterol; Ezetimibe
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2020.12.023

Many patients with hypercholesterolemia fail to achieve sufficient low-density lipoprotein cholesterol (LDL-C) lowering despite use of guideline-recommended lipid-lowering therapies. This study evaluated LDL-C lowering with the combination of bempedoic acid, ezetimibe, and atorvastatin. This was a phase 2, randomized, double-blind, placebo-controlled study (NCT03051100). After washout of lipid-lowering drugs, patients were randomized 2:1 to triple therapy (bempedoic acid 180 mg, ezetimibe 10 mg, and atorvastatin 20 mg; n = 43) or placebo (n = 20) once daily for 6 weeks. The primary endpoint was percent change from baseline in LDL-C at week 6. Mean age for the 63 randomized patients was 61.2 years; baseline LDL-C was 154.8 mg/dL. At week 6, mean LDL-C lowering with triple therapy (−63.6%) was significantly greater than with placebo [–3.1%; difference, −60.5% [(95% CI, −68.0% to −53.0%); p < 0.001]. Significant reductions with triple therapy vs. placebo were also observed for non–high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein (p < 0.001 for all). With triple-therapy, 90% of patients achieved LDL-C <70 mg/dL and 95% of patients had ≥50% lower LDL-C from baseline to week 6; no patients in the placebo group met either goal. The majority of treatment-emergent adverse events were mild to moderate in severity. No patients experienced clinically relevant elevations in aminotransferase or creatine kinase levels. Among patients with hypercholesterolemia, the combination of bempedoic acid, ezetimibe, and atorvastatin significantly lowered LDL-C, allowing more than 90% of patients in this study to reach guideline-recommended LDL-C goals. [Display omitted] •Many patients require combination therapy to achieve low-density lipoprotein cholesterol (LDL-C) goals.•Phase 2 study evaluating bempedoic acid, ezetimibe, and atorvastatin triple therapy.•Triple therapy significantly lowered LDL-C levels by 60.5% vs placebo.•More than 90% of patients achieved LDL-C <70 mg/dL with triple therapy.•Triple therapy was generally well-tolerated.