Comprehensive review of statin-intolerance and the practical application of Bempedoic Acid

Abstract

Statin-intolerance (SI) has prevalence between 8.0 % and 10 %, and muscular complaints are the most common reason for discontinuation. Bempedoic acid (BA), an ATP citrate lyase inhibitor, decreases hepatic generation of cholesterol, upregulates low-density lipoprotein (LDL) receptor expression in the liver, and eventually clears circulating LDL-cholesterol from the blood. Multiple randomized clinical trials studying BA demonstrate a reduction in LDL levels by 17-28 % in SI. The CLEAR OUTCOME trial established significant cardiovascular benefits with BA. A dose of 180 mg/day of BA showed promising results. BA alone or in combination with ezetimibe is US Food and Drug Administration-approved for use in adults with heterozygous familial hypercholesterolemia and/or established atherosclerotic cardiovascular disease. BA reduced HbA1c by 0.12 % (p < 0.0001) in patients with diabetes. Adverse events of BA include myalgia (4.7 %), anemia (3.4 %), and increased aminotransferases (0.3 %). BA can cause up to four times higher risk of gout in those with a previous gout diagnosis or high serum uric acid levels. Reports of increased blood urea nitrogen and serum creatinine were noted. Current evidence does not demonstrate a reduction in deaths from cardiovascular causes. More studies that include a diverse population and patients with both high and low LDL levels should be conducted. We recommend that providers consider BA as an adjunct to statin therapy in patients with a maximally tolerated dosage to specifically target LDL levels.

Keywords: Bempedoic acid; Lipid lowering therapies; Low-density lipoprotein cholesterol; Statin-intolerance.