In higher-risk, statin-intolerant adults with diabetes, bempedoic acid reduced MACE at a median 3 y
An ACP Journal Club commentary noted that it's unknown whether lower-risk and younger statin-intolerant patients would derive the degree of benefit from bempedoic acid found in this study, since the industry-funded trial enrolled only high-risk and older patients.
Bempedoic acid was effective in reducing major adverse cardiovascular events (MACEs) in patients with diabetes and it did not increase the rate of new-onset diabetes in patients without the disease at baseline, according to a new analysis of a pharma-funded trial. Diabetes patients who couldn't tolerate statins and were randomized to bempedoic acid had a 2.4% absolute reduction in risk of cardiovascular (CV) death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization versus those on placebo, according to subgroup results from the CLEAR trial.
The study was published by The Lancet Diabetes & Endocrinology on Dec. 4, 2023. The following commentary by Michelle Kelsey, MD and L. Kristin Newby, MD, MHS, was published in the ACP Journal Club section of Annals of Internal Medicine on April 2.
In this prespecified secondary analysis of the CLEAR Outcomes trial, Ray and colleagues showed reduced risk for MACE with bempedoic acid compared with placebo in patients with diabetes. This benefit was not accompanied by an increase in hemoglobin A1c—an effect that can occur with statin therapy.
Although the mechanism is not entirely understood, statin use has been associated with a small, dose-dependent increase in blood glucose and increased risk for new-onset type 2 diabetes. The CV benefit of statins has been shown to outweigh these metabolic changes. Because of this, and in the absence of head-to-head comparison studies, statins remain the first-line agents for lipid-lowering therapy. However, in patients with confirmed intolerance to statins, bempedoic acid can be a useful alternative as an oral medication, without potential metabolic side effects.
Some features of the CLEAR Outcomes trial limit the generalizability of these results to all patients with diabetes. First, patients had to show tolerability and adherence during a 4-week placebo run-in period before randomization. This may have altered the population under study. Second, CLEAR Outcomes enrolled only patients with previous CV events, or patients with elevated risk scores, coronary artery calcium score >400 Agaston units, women aged >65 years with diabetes, or men aged >60 years with diabetes. It is unknown whether patients at lower risk or younger patients with diabetes would derive the same degree of benefit from bempedoic acid. Finally, CLEAR Outcomes followed up patients for a median 3.4 years, but patients often continue to receive lipid-lowering therapy for many years for CV risk reduction.
Research in other groups and with longer duration of treatment will help to clarify the role of bempedoic acid within the broader population.