Bempedoic acid beneficial for prevention of cardiac events in high-risk patients

The use of bempedoic acid in primary prevention appears to lower the incidence of major cardiovascular events for high-risk patients, as shown in the subgroup analysis of the CLEAR Outcomes* trial.

CLEAR Outcomes included 13,970 statin-intolerant patients with a low-density lipoprotein cholesterol (LDL-C) level of at least 100 mg/dL who had been randomly assigned to receive either oral bempedoic acid 180 mg or matching placebo daily for primary prevention. The current analysis included a subgroup of 4,206 patients (intervention: n=2,100; control: n=2,106) at high risk for a first cardiovascular event, characterized as a coronary artery calcium score of at least 400 Agatston units or the presence of either type 1 or 2 diabetes in women older than 65 years or men older than 60 years.

The mean age of the subgroup was 68 years, with the majority being women (59 percent) and having diabetes (66 percent). Compared with placebo, bempedoic acid reduced LDL-C levels by 30.2 mg/dL (21.3 percent) and high-sensitivity C-reactive protein levels by 0.56 mg/L (21.5 percent).

Over a median follow-up of 39.9 months, the primary endpoint of the time from randomization to the first occurrence of any component of a composite of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization was significantly lower in the bempedoic acid arm than in the placebo arm (5.3 percent vs 7.6 percent; adjusted hazard ratio [HR], 0.70, 95 percent confidence interval [CI], 0.55–0.89; p=0.002).

The same was true for the key secondary endpoints: the composite of cardiovascular death, MI, or stroke (4.0 percent vs 6.4 percent; HR, 0.64, 95 percent CI, 0.48–0.84; p<0.001); MI (1.4 percent vs 2.2 percent; HR, 0.61, 95 percent CI, 0.39–0.98); cardiovascular death (1.8 percent vs 3.1 percent; HR, 0.61, 95 percent CI, 0.41–0.92); and all-cause mortality (3.6 percent vs 5.2 percent; HR, 0.73, 95 percent CI, 0.54–0.98). Bempedoic acid showed no significant effect on stroke or coronary revascularization compared with placebo.

Adverse effects that occurred among patients who received bempedoic acid vs placebo included a higher incidence of gout (2.6 percent vs 2.0 percent), cholelithiasis (2.5 percent vs 1.1 percent), and increases in serum creatinine, uric acid, and hepatic enzyme levels.

*Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen