For patients with hypercholesterolemia who are intolerant to statins, bempedoic acid may be a safe and effective therapy to aid in lowering LDL levels, according to findings presented at the American Heart Association Scientific Sessions.

“Bempedoic acid (Esperion Therapeutics) is a first-in-class small molecule inhibitor of ATP citrate lyase, an enzyme upstream of HMG-CoA reductase in cholesterol biosynthesis, which is inactive in skeletal muscle,” Ulrich Laufs, MD, PhD, of the department of cardiology at Leipzig University, Germany, and colleagues wrote in an abstract. “This phase 3 study evaluated the efficacy and safety of bempedoic acid in statin-intolerant patients.”

The researchers conducted a randomized, double-blind, placebo-controlled study of 345 adult primary and secondary prevention patients with hypercholesterolemia and a history of intolerance to at least two statins (mean age, 65 years; 56% women; mean LDL, 158 mg/dL; median high-sensitivity C-reactive protein, 2.9 mg/L).

All participants engaged in a 4-week period in which they took only the placebo before being randomly assigned to 180 mg per day of bempedoic acid (n = 234) or placebo (n = 111) for 24 weeks.

The primary endpoint was mean percentage change in LDL from baseline to 12 weeks.

According to the researchers, the bempedoic acid group had a greater lowering of LDL at 12 weeks than the placebo group (P < .001). High-sensitivity CRP was also reduced in the bempedoic acid group vs. the placebo group at 12 weeks (P < .001). These reductions remained at week 24.

Adverse effects from treatment were observed in 64.1% of patients taking bempedoic acid and in 56.8% of those taking placebo. Most commonly, patients experienced musculoskeletal disorders (bempedoic acid, 22.2%; placebo, 25.2%), infections (bempedoic acid, 17.5%; placebo, 22.5%), gastrointestinal complaints (bempedoic acid, 10.7%; placebo, 11.7%) and myalgia (bempedoic acid, 4.7%; placebo, 7.2%).

“In statin-intolerant patients with hypercholesterolemia, bempedoic acid reduced LDL-C by 21% and hsCRP by 24% with a side effect profile similar to placebo,” the researchers wrote in the abstract. “Therefore, bempedoic acid may provide a complementary oral therapy for LDL-C lowering.”

Bempedoic acid is not yet approved for use in the United States. According to a press release from Esperion Therapeutics, the company plans to send applications to the FDA in the first quarter of 2019 for approval of bempedoic acid and a bempedoic acid/ezetimibe combination for LDL lowering. – by Melissa J. Webb

Reference:

Laufs U, et al. LBP.01 – At the Forefront of Risk Reduction. Presented at: American Heart Association Scientific Sessions; Nov. 10-12, 2018; Chicago.