Long-Term Safety and Efficacy of Bempedoic Acid for Lowering LDL-C in ASCVD, HeFH

During an open-label extension trial, bempedoic acid was well tolerated and had sustained efficacy for lowering low-density lipoprotein cholesterol (LDL-C) up to 2.5 years. These findings were published in the American Journal of Cardiology.

This trial was an extension of the phase 3 Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen Harmony (CLEAR Harmony OLE; Clinicatrials.gov identifier: NCT03067441) study conducted in Europe and North America between 2017 and 2019. Patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) were randomly assigned to receive bempedoic acid (n=1488) or placebo (n=742) for 52 weeks. During the open-label extension, 970 patients continued receiving bempedoic acid and 492 switched from placebo to bempedoic acid for 78 weeks. Safety and efficacy were evaluated at a 4-week follow-up at week 82.

The entire extension population was aged mean 66.9±8.7 years, 73.9% were men, BMI was 29.5±5.0, 96.5% were White, 96.3% had ASCVD, 3.7% had HeFH, baseline LDL-C was 101.6±28.2 mg/dL, and statin intensity was high among 55.5%.

Treatment-emergent adverse events occurred among 78% of both patient cohorts, stratified by bempedoic acid use for 130 or 78 weeks. The most common events were muscle spasms, myalgia, pain in extremities, arthralgia, and dizziness. The most common events leading to discontinuation (7.8%) were myalgia and muscle spasms.

Pre-specified adverse events of special interest included gout (2.6%) and new-onset or worsening diabetes (5.5%).

No new safety signals were observed during the extension period.

The decrease in LDL-C (-14.2%) remained stable during the extension period compared with the initial trial (mean, -16.0 mg/dl) among the patients who continued bempedoic acid and was similar (-14.5%) among those who switched from placebo (mean, -16.1 mg/dl).

Bempedoic acid was also associated with stable decreases in non-high-density lipoprotein cholesterol (-11%), apolipoprotein B (-7%), total cholesterol (-10%), and high-sensitivity C-reactive protein (-17%).

This study may have been limited by the imbalance among patients who continued and switched therapy.

“Overall, findings from the CLEAR Harmony OLE study support other reports on the safety and efficacy of bempedoic acid for the treatment of hypercholesterolemia and demonstrate that safety and efficacy are maintained for up to 130 weeks in patients with ASCVD and/or HeFH,” the study authors wrote.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Ballantyne CM, Banach M, Bays HE, et al. Long-term safety and efficacy of bempedoic acid in patients With atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia (from the CLEAR Harmony Open-Label Extension Study). Am J Cardiol. Published online April 25, 2022. doi:10.1016/j.amjcard.2022.03.020