Does bempedoic acid reduce the likelihood of cardiovascular events in high-risk patients with hyperlipidemia?
Bempedoic acid provides a reduction in nonfatal MI and the need for coronary revascularization without changing mortality. In the primary prevention population, the number needed to treat to prevent one event was 42.
Randomized controlled trial (double-blinded)
Bempedoic acid is a prodrug that when activated in the liver reduces cholesterol synthesis and has been shown to reduce low-density lipoprotein (LDL) cholesterol levels by 17% to 28% in previous studies. In this study, patients with a previous cardiovascular event (n = 9764) or who were at elevated risk for cardiovascular events (n = 4206) at one of 1250 sites in 32 countries were randomized to receive bempedoic acid 180 mg daily or placebo. All patients had to confirm that they were statin-intolerant before randomization; other lipid-lowering drugs, such as ezetimibe, niacin, or PCSK9 inhibitors, could be continued. Prior to randomization, each patient had to confirm at least 80% adherence to and tolerance of a placebo in a 30-day run-in period, biasing the results in favor of the drug. After 6 months, patients whose LDL cholesterol level had increased at least 25% were counseled regarding diet, and, if the increase persisted, their other cholesterol-lowering drugs could be adjusted. Groups were balanced at baseline with a mean age of 65 years, 48% were women, the mean LDL level was 139 mg/dL, 70% had a prior myocardial infarction (MI), and 46% had diabetes (including 20% with uncontrolled diabetes). Patients who tolerated a very low daily dose of statin were allowed in the trial and constituted 22% of each group; 11.5% were taking ezetimibe. The primary outcome was a composite of cardiovascular death, nonfatal stroke, nonfatal MI, or coronary revascularization and was assessed after a median follow-up of 41 months. This composite was less likely in the bempedoic acid group (11.7% vs 13.3%; P = .004; number needed to treat = 62 for 41 months). This was driven primarily by significant reductions in fatal or nonfatal MI (3.7% vs 4.8%) and coronary revascularization (6.2% vs 7.6%). There was no difference in cardiovascular (3.8% vs 3.7%) or all-cause (6.2% vs 6.0%) mortality. Of particular relevance for primary care clinicians, the hazard ratio (HR) for the primary composite endpoint was actually a bit more favorable for the primary prevention patients (HR 0.68; 95% CI 0.53 - 0.87) than for the secondary prevention patients (HR 0.91; 0.82 - 1.01). Myalgias occurred at similar rates in the treatment and placebo groups (6.8% vs 5.6%). Premature discontinuation was approximately 30% in both groups, which seems high and may be because this population is generally intolerant of medications.
Mark H. Ebell, MD, MS
University of Georgia