Bempedoic Acid Decreases Lipid Levels Among Patients With Hyperlipidemia

A systematic review and meta-analysis have shown bempedoic acid modestly reduced lipid levels among patients with hyperlipidemia, with a favorable toxicity profile. The study findings were presented during the American College of Cardiology annual meeting, held virtually May 15-17, 2021.

Researchers from Maimonides Medical Center in Brooklyn, New York, searched publication databases for phase 3 randomized clinical trials of bempedoic acid. Mean decrease in lipid levels after therapy with bempedoic acid, an inhibitor of cholesterol biosynthesis through inhibition of ATP citrate lyase (ACL), was assessed. Inhibition of ACL is useful in the treatment of hyperlipidemia.

A total of 4 trials were included in this analysis, comprising 3542 patients who were randomized to receive bempedoic acid (n=2361) or placebo (n=1182).

Compared with patients randomized to placebo, after 12 weeks of bempedoic acid therapy, patients’ levels of low-density lipoprotein cholesterol (LDL-C) were decreased by 20% from baseline (mean difference [MD], -20.62%; 95% CI, -24.27 to -16.98; P <.00001; I², 77%).

Non-high-density lipoprotein cholesterol (HDL-C) decreased by 16% from baseline (MD, -16.37%; 95% CI, -20.16 to -12.59; P <.00001; I², 83%) and total cholesterol decreased by 13% (MD, -13.39%; 95% CI, -16.09 to -10.69; P <.00001; I², 81%).

In addition, apolipoprotein B decreased by 14% from baseline after 12 weeks of bempedoic acid therapy, compared with placebo (MD, -14.30%; 95% CI, -17.05 to -11.56; P <.00001; I², 72%), and high sensitivity C-reactive protein levels decreased by about 18% (MD, -17.98%; 95% CI, -27.06 to -8.90; P =.00001; I², 72%) .

Treatment with bempedoic acid was associated with increased risk for gout (odds ratio [OR], 3.56; 95% CI, 1.50-8.43; P =.004; I², 0%) but not for new onset or worsening diabetes mellitus (OR, 0.69; 95% CI, 0.49-0.97; P =.03; I², 0%), myalgias (OR, 0.92; 95% CI, 0.67-1.26; P =.61; I², 0%), urinary tract infections (OR, 1.17; 95% CI, 0.21-6.44; P =.86; I², 78%), or elevated liver function tests (OR, 2.53; 95% CI, 0.79-8.11; P =.12; I², 0%).

This meta-analysis was likely biased by the significant heterogeneity detected among the underlying studies.

These data indicated that interruption of fatty acid synthesis by therapy with bempedoic acid modestly decreased lipid levels among patients with hyperlipidemia. Except for gout, bempedoic acid treatment was not associated with an increased risk of toxic effects.

Reference

Farooqui A, Maheshwari S, Uddin S, et al. Meta-analysis of phase III randomized controlled trials evaluating bempedoic acid: a novel treatment agent for hyperlipidemia. Presented at: American College of Cardiology 2021 Annual Meeting, May 15-17, 2021. Abstract.