Bempedoic acid tied to primary prevention of cardiovascular events in statin-intolerant patients: JAMA

Four thousand two hundred six participants with high cardiovascular risk but without a prior cardiovascular event were enrolled in the study published in JAMA (Journal of the American Medical Association). The researchers found that treatment with 180 mg daily bempedoic acid in this subgroup was associated with significantly reduced MACE (hazard ratio, 0.70).

The CLEAR Outcomes trial reported CV (cardiovascular) outcomes in a mixed population of primary and secondary prevention patients unwilling or unable to take guideline-recommended statins. Among the 13 970 patients the trial enrolled, 30% (4206) had characteristics associated with a high risk of adverse cardiovascular outcomes but without a prior event.

Current guidelines recommend statins for administration to high-risk patients for a first major adverse cardiovascular event (primary prevention). However, the current recommendations are predominantly derived from clinical trials conducted several decades ago during the initial development of statins for reducing LDL-C (low-density lipoprotein cholesterol) levels.

Recent data are limited on the effects of statins or other adjunctive treatments in patients without a history of a cardiovascular event, bringing into question whether the benefits of cholesterol-lowering exceed the harms in these patients. Lipid-lowering therapies are underutilized in high-risk primary prevention patients, specifically patients and women from racial and ethnic minority populations. More than half of eligible patients fail to receive lipid-lowering therapies.

Against the above background, Steven E. Nissen, Cleveland Clinic, Cleveland, Ohio, and colleagues aimed to determine the effects of bempedoic acid on cardiovascular outcomes in primary prevention patients.

Thirteen thousand nine hundred seventy statin-intolerant patients were enrolled in masked, randomized clinical trials, including 4206 primary prevention patients. Participants were randomized to 180 mg daily oral bempedoic acid (n = 2100) or a matching placebo (n = 2106). The mean participants' age was 68 years, 59% were female, and 66% had diabetes.

The primary efficacy measure was determined by the time from randomization to the first occurrence of any composite component of nonfatal myocardial infarction (MI), cardiovascular death, coronary revascularization, or nonfatal stroke.

The study revealed the following findings:

• From a mean baseline of 142.5 mg/dL, compared with placebo, bempedoic acid reduced LDL cholesterol levels by 30.2 mg/dL (21.3%) and high-sensitivity C-reactive protein levels by 0.56 mg/L (21.5%), from a median baseline of 2.4 mg/L.
• Follow-up for a median of 39.9 months was associated with a significant risk reduction for the primary endpoint (111 events [5.3%] vs 161 events [7.6%]; adjusted hazard ratio [HR], 0.70) and key secondary endpoints, including the composite of cardiovascular death, MI, or stroke (83 events [4.0%] vs 134 events [6.4%]; HR, 0.64); MI (29 events [1.4%] vs 47 events [2.2%]; HR, 0.61); cardiovascular death (37 events [1.8%] vs 65 events [3.1%]; HR, 0.61); and all-cause mortality (75 events [3.6%] vs 109 events [5.2%]; HR, 0.73).
• There was no significant effect on stroke or coronary revascularization.
• Adverse effects with bempedoic acid included a higher incidence of gout (2.6% vs 2.0%), cholelithiasis (2.5% vs 1.1%), and increases in serum creatinine, uric acid, and hepatic enzyme levels.

"Bempedoic acid significantly reduced the primary composite endpoint, nonfatal MI, time to death from cardiovascular causes, coronary revascularization, or nonfatal stroke in primary prevention patients unable to tolerate recommended statins doses," the researchers wrote. "Treatment was also associated with significant reductions in cardiovascular death, myocardial infarction, and all-cause mortality."

Reference:

Nissen SE, Menon V, Nicholls SJ, et al. Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients. JAMA. Published online June 24, 2023. doi:10.1001/jama.2023.9696