Bempedoic acid, an investigational adenosine triphosphate citrate lyase inhibitor, might safely lower low-density lipoprotein (LDL) cholesterol levels when added to statin therapy, according to study results published in the New England Journal of Medicine.

Previous short-term studies have reported decreased LDL cholesterol levels following treatment with bempedoic acid. The small molecule inhibits a key enzyme in the cholesterol biosynthesis pathway, thus leading to lower LDL cholesterol. Bempedoic acid is a prodrug that requires activation by a liver enzyme absent in most peripheral tissues, making it unique from statins because of its liver-specific action.

Researchers conducted a randomized controlled trial of 2230 patients with atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia. All patients had LDL cholesterol levels ≥70 mg/dL while treated with maximally tolerated statin therapy. Participants were randomly assigned to receive bempedoic acid (1488 patients) or placebo (742 patients) for 1 year in addition to their statin regimen.

The rate of adverse events, the primary outcome of this study, was nearly identical in both groups (78.5% in the bempedoic acid group and 78.7% in the placebo group). The rate of serious adverse events was also not substantially different (14.5% and 14.0%, respectively). However, adverse events leading to treatment discontinuation were more common with bempedoic acid (10.9% vs 7.1%, respectively).

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The occurrence of muscle-related adverse events was similar in both groups, however, the incidence of gout was significantly higher in those treated with bempedoic acid (1.2% vs 0.3%; P =.03).

When added to mostly moderate-intensity or high-intensity statin therapy, treatment with bempedoic acid led a 19 mg/dL reduction in LDL cholesterol levels after 12 weeks, whereas levels generally stayed the same with placebo (P <.001). This reduction is similar in magnitude to reductions reported after adding ezetimibe to statin therapy.

“[T]reatment with bempedoic acid added to maximally tolerated statin therapy did not lead to a higher overall incidence of adverse events than placebo and led to significantly lower LDL cholesterol levels,” concluded the authors.

This study was funded by Esperion Therapeutics.

ReferenceRay KK, Bays HE, Catapano AL, et al. Safety and efficacy of bempedoic acid to reduce LDL cholesterol. N Engl J Med. 2019;380:1022-1032.