Efficacy and Safety of Bempedoic Acid

In the prespecified analysis of a randomized, double-blind, placebo-controlled trial, bempedoic acid reduces LDL cholesterol, high-sensitivity C-reactive protein, and risk of cardiovascular events among those with baseline diabetes, prediabetes, or normoglycemia, with or without cardiovascular disease at baseline. Between Dec 22, 2016, and Nov 7, 2022, 13 970 patients who were unwilling or unable to take guideline-recommended doses of statins and an LDL cholesterol of 2·59 mmol/L or more were randomized to either bempedoic acid 180 mg once daily or placebo (45·6% with diabetes, 41·5% with prediabetes, and 12·9% with normoglycemia). Over a median of 3·4 years follow up, patients with diabetes had significant cardiovascular risk reductions in the composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization with bempedoic acid (HR 0·83; absolute risk reduction of 2·4%) compared to placebo, with no statistical evidence of effect modification across glycemic strata. The proportion of patients who developed new-onset diabetes were similar between the bempedoic acid and placebo groups (11·1% with bempedoic acid versus 11·5% with placebo; HR 0·95). HbA_1c concentrations at month 12 and the end of the study were similar between randomized groups in patients who had prediabetes and normoglycemia. Placebo-corrected LDL cholesterol concentrations and high-sensitivity C-reactive protein at 6 months were reduced in each glycemic stratum (diabetes, prediabetes, and normoglycemia) for patients randomly assigned to bempedoic acid. Statins increase the risk of diabetes in a dose-dependent manner. Consistent with genetic studies, bempedoic acid does not increase the risk of new-onset diabetes nor worsen measures of glycaemia among those without diabetes, although it inhibits ATP citrate lyase, an enzyme in the same pathway as the target for statins. Source: https://www.thelancet.com/