Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance.

Laufs U, Banach M, Mancini GBJ, Gaudet D, Bloedon LT, Sterling LR, Kelly S, Stroes ESG. Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance. J Am Heart Assoc. 2019 Apr 2;8(7):e011662. doi: 10.1161/JAHA.118.011662. PMID: 30922146; PMCID: PMC6509724.

Abstract

Background Inability to tolerate statins because of muscle symptoms contributes to uncontrolled cholesterol levels and insufficient cardiovascular risk reduction. Bempedoic acid, a prodrug that is activated by a hepatic enzyme not present in skeletal muscle, inhibits ATP -citrate lyase, an enzyme upstream of β-hydroxy β-methylglutaryl-coenzyme A reductase in the cholesterol biosynthesis pathway. Methods and Results The phase 3, double-blind, placebo-controlled CLEAR (Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen) Serenity study randomized 345 patients with hypercholesterolemia and a history of intolerance to at least 2 statins (1 at the lowest available dose) 2:1 to bempedoic acid 180 mg or placebo once daily for 24 weeks. The primary end point was mean percent change from baseline to week 12 in low-density lipoprotein cholesterol. The mean age was 65.2 years, mean baseline low-density lipoprotein cholesterol was 157.6 mg/dL, and 93% of patients reported a history of statin-associated muscle symptoms. Bempedoic acid treatment significantly reduced low-density lipoprotein cholesterol from baseline to week 12 (placebo-corrected difference, -21.4% [95% CI, -25.1% to -17.7%]; P<0.001). Significant reductions with bempedoic acid versus placebo were also observed in non-high-density lipoprotein cholesterol (-17.9%), total cholesterol (-14.8%), apolipoprotein B (-15.0%), and high-sensitivity C-reactive protein (-24.3%; P<0.001 for all comparisons). Bempedoic acid was safe and well tolerated. The most common muscle-related adverse event, myalgia, occurred in 4.7% and 7.2% of patients who received bempedoic acid or placebo, respectively. Conclusions Bempedoic acid offers a safe and effective oral therapeutic option for lipid lowering in patients who cannot tolerate statins.

Summary:

About 7-29% of patients who take statins report statin intolerance, and greater than 90% of statin-related side effects reported are muscle symptoms. One of these people is the patient from my third H&P, who stated that her doctor stopped her statin medication due to the side effects. However, stopping medication is not an effective solution since high cholesterol/ lipids can lead to major health problems, such as cardiovascular disease and stroke. Bempedoic acid, the first in it’s class, is a small molecule inhibitor of ATP citrate-lyase. Bempedoic acid acts on the same pathway as statins, however it lacks the activating enzyme in skeletal muscle, thus preventing muscle-related adverse effects. This study tested the effects of bempedoic acid on lowering cholesterol. The participants were 345 people with history of cholesterelemia and statin intolerance. It found that bempedoic acid was effective in significantly lowering LDL, non-HDL cholesterol, total cholesterol, apolipoprotein B, and CRP. It was found to be generally well tolerated- only 4.7% of participants receiving bempedoic acid reported muscle related pain, which compared to 7.2% receiving placebo (and compared to 100% of people included in the trial). Thus, bempedoic acid is a safe and effective alternative for lowering cholesterol in patients who cannot tolerate statins. 

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