The title of the article is Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance. The article was published in the Journal of the American Heart Association in March 2019. The first author is Ulrich Laufs. The objective of the study is to evaluate the efficacy, safety, and tolerability of bempedoic acid 180mg daily in patients who can’t tolerate statin therapy for primary or secondary prevention of cardiovascular events.
Bempedoic acid is a prodrug that’s activated by liver enzymes not present in skeletal muscle. Once activated, it inhibits an enzyme, ATP-citrate lyase, in the cholesterol synthesis pathway. Statin also targets this enzyme. Therefore, it helps reduce LDL-C while preventing the muscular adverse effects associated with statins because the activating enzyme is not found in skeletal muscle.
In this phase 3 clinical trial, 345 patients with high cholesterol and a history of intolerance to at least 2 statins were randomly assigned in 2:1 ration, to take bempedoic acid 180mg or placebo. The primary outcome of the study was the mean percent change of LDL-C in 12 weeks.
The study found that bempedoic acid reduced LDL-C significantly more than placebo at week 12. They notice the reduction in week 4, and it’s maintained throughout the study. There is an average of 21.4% reduction in LDL-C. The reduction in non-HDL-C is 21.1% and in total cholesterol is 14.8%. The improvement was maintained at week 24. Changes in triglyceride and HDL-C were minimal.
Adverse events occurred n 64% of patients taking bempedoic acid and 56.85 of patients taking placebo. The majority of the adverse events in both groups were mild or moderate intensity. The most common adverse events were musculoskeletal and connective tissue disorder (22.2% bemedoic acid, 25.2% placebo), infections, and infestations (17.5% bempedoic acid, 22.5% placebo), and GI disorders (10.7% bempedoic acid, 11.7% placebo). No serious muscle-related adverse events occurred during the study. The most common event was myalgia, experienced by 4.7% in bempedoic acid patients and 7.2% in placebo patients.
Muscle-related symptoms were not increased relative to placebo, which confirms the expectation that bempedoic acid does not induce muscle-related side effects. Patients in bempedoci acid treatment group did experience a small elevation in mean uric acid levels, but the rate of gout was low (1.7%).
The limitation of the study is that it only followed patients for 24 weeks. The clinical bottom line is that bempedoci acid is effective in reducing LDL-C and has a more favorable side-effect profile. It can be used as an alternative or adjunct therapy for patients who can’t tolerate statins.
