A fixed-dose combination of bempedoic acid with ezetimibe added to high-intensity statin therapy in patients suffering from hypercholesterolemia and high cardiovascular disease (CVD) risk lowered low-density lipoprotein cholesterol (LDL-C) levels, according to results from a recent clinical trial published in European Journal of Preventive Cardiology.
In this phase 3, double-blind, multicenter clinical trial, study investigators evaluated combination bempedoic acid (180 mg) and ezetimibe (10 mg) for efficacy and safety compared with placebo and each therapy alone. The participants were adults receiving maximally tolerated statin therapy and previously identified as high-risk due to atherosclerotic CVD, heterozygous familial hypercholesterolemia, and other risk factors related to CVD (eg, family history of chronic heart disease, smoking, and low high-density lipoprotein cholesterol).
Between October 23, 2017, and July 3, 2018, study investigators randomly assigned 382 participants from 78 sites in the United States to 4 groups: combined bempedoic acid and ezetimibe (n=108), bempedoic acid (n=110), ezetimibe (n=109), or placebo (n=55). The primary study end point was the percentage change in LDL-C from baseline to week 12. Study investigators identified coprimary end points as the available comparisons between each treatment arm. Study investigators recorded each participant’s baseline LDL-C, then reviewed the levels at weeks 4, 8, and 12.
Due to data integrity concerns regarding 81 participants from the same clinical franchise in 1 metropolitan area, study investigators included only 301 participants in the primary analysis.
At week 12, study investigators found that 33.7% of participants in the bempedoic acid with ezetimibe group had a 50% or greater reduction in LDL-C levels from baseline when compared with placebo, ezetimibe, and bempedoic acid groups (0%, 5.0%, and 3.7%, respectively; P <.001).
Bempedoic acid with ezetimibe reduced LDL-C levels to less than 2.6 mmol/L (100 mg/dL) (67.5%) or less than 1.8 mmol/L (70 mg/dL) (31.3%) at week 12 compared with placebo (17.5% and 0%, respectively; P <.001).
The lowering power of the fixed-dose combination was also significant in comparison with the ezetimibe group at the above-mentioned LDL-C levels (42.5% and 10.0%, respectively; P ≤.002) and the bempedoic acid group (43.9% and 6.1%, respectively; P ≤.003).
Study limitations included the study’s relatively short duration, an imbalance in baseline demographics between treatment groups, and protocol issues connected to having to exclude 81 participants in 1 metropolitan area.
Study investigators reported that the fixed-dose combination of bempedoic acid with ezetimibe lowered LDL-C in patients who were receiving high-intensity statin therapy, including those patients who were statin-intolerant. They concluded by noting that as clinical practice guidelines shift to target lowering LDL-C levels, bempedoic acid with ezetimibe “may help provide a potent and convenient therapy complementary to existing lipid-modifying therapy regimens.”
Disclosures: This study was supported by Esperion Therapeutics Inc. Please see the original reference for a full list of authors’ disclosures.
Ballantyne CM, Laufs U, Ray KK, et al. Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy [published online July 29, 2019]. Eur J Prev Cardiol. doi: 10.1177/2047487319864671