Is bempedoic acid effective for secondary prevention of cardiovascular disease?

Abstract

Listen

Translate article

Bempedoic acid is a cholesterol-lowering drug approved for reduction of the risk of myocardial infarction (MI) and coronary revascularization in adults who are unable to take recommended statin therapy with established cardiovascular disease (CVD), or at high risk for a CVD event but without established CVD. However, reduction of CV events by bempedoic acid in patients with documented CVD is modest and not statistically significant. The CLEAR Outcomes trial is the largest randomized trial of bempedoic acid including 13,970 patients; 70% of whom had documented CVD (secondary prevention cohort), and 30% were considered high CV risk but without established CV disease (primary prevention cohort). The primary outcome of the CLEAR OUTCOMES trial was a composite of death from CV causes, nonfatal MI, nonfatal stroke, or coronary revascularization (MACE-4). After a median follow-up of 40.6 months, the incidence of CV event was significantly decreased in the bempedoic group versus the placebo group in the whole study population; hazard ratio (HR) 0.87; 95% CI, 0.79 to 0.96; P=0.004). However, this decrease in CV events was mainly driven by the reduction of MACE-4 in the primary prevention cohort; HR 0.68 (95% CI, 0.53 to 0.87), whereas the corresponding reduction in the secondary prevention cohort was more modest; HR 0.91 (95% CI 0.82 to 1.01), Pinteraction=0.03. Results of a post-hoc analysis of the CLEAR Outcomes trial suggested possible increase in all-cause mortality; risk ratio (RR) 1.15 and CV mortality RR 1.21 in the secondary prevention patients. Conversely, in the primary prevention group, there was decrease in all-cause mortality RR 0.70 and CV mortality RR 0.58. While the investigators of the CLEAR Outcomes trial published results of the primary prevention group separately, they did not report those results in the larger secondary group despite greater number of CV events. A randomized trial evaluating bempedoic acid in patients with documented CVD is required to clarify its efficacy and safety in this group of patients. Until such trial is available, the use of bempedoic acid is not recommended for secondary prevention of CV disease.