Treatment of statin-intolerant patients with bempedoic acid was associated with a lower risk of major adverse cardiovascular events, including death from cardiovascular causes, nonfatal myocardial infarction (MI), nonfatal stroke or coronary revascularization, based on results from the CLEAR OUTCOMES trial presented at ACC.23/WCC in New Orleans and simultaneously published in the New England Journal of Medicine (NEJM).

The trial randomized 13,970 patients to receive either bempedoic acid (180 mg orally; n=6,992) or placebo (n=6,978). All patients were statin intolerant and had, or were at high risk for, cardiovascular disease. The mean LDL-C level at baseline was 139.0 mg/dL in both groups and the median duration of follow-up was 40.6 months.

Overall results found the incidence of a major cardiovascular event (the primary endpoint) was significantly lower with bempedoic acid than with placebo (819 patients [11.7%] vs. 927 [13.3%]). Similarly, the incidences of a composite of death from cardiovascular causes, nonfatal stroke or nonfatal MI (575 [8.2%] vs. 663 [9.5%]); fatal or nonfatal MI (261 [3.7%] vs. 334 [4.8%]); and coronary revascularization (435 [6.2%] vs. 529 [7.6%]) were also lower in the bempedoic group compared with the placebo group. However, incidences of gout and cholelithiasis were higher with bempedoic acid than with placebo, as were the incidences of small increases in serum creatinine, uric acid, and hepatic-enzyme levels.

According to researchers, no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause were observed in the bempedoic acid group. They also noted that at six months from baseline, the reduction in LDL-C level was greater with bempedoic acid than with placebo by 29.2 mg/dL. The observed difference in the percent reductions was 21.1 percentage points in favor of bempedoic acid, they said.

"Statins are the cornerstone of risk reduction in patients with elevated LDL cholesterol," said Steven E. Nissen, MD, MACC, chief academic officer of the Heart Vascular and Thoracic Institute at Cleveland Clinic and chair of the study. "Most people can take statins, but some cannot. This is the first study that directly addressed the problem of statin-intolerant patients. We achieved what we hoped we would get – a very positive result in a population of people who just could not tolerate statins."

In a related editorial comment also published in NEJM, John H. Alexander, MD, MHS, FACC, writes that while there are a couple of observations from CLEAR Outcomes that warrant further exploration, "bempedoic acid has now entered the list of evidence-based alternatives to statins for primary and secondary prevention in patients at high cardiovascular risk." He notes that "the benefits of bempedoic acid are now clearer, and it is now our responsibility to translate this information into better primary and secondary prevention for more at-risk patients, who will, as a result, benefit from fewer cardiovascular events."

Clinical Topics: Dyslipidemia, Nonstatins, Novel Agents, Statins

Keywords: ACC Annual Scientific Session, ACC23, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Dicarboxylic Acids, ACC.23/WCC Meeting Newspaper, ACC Scientific Session Newspaper

< Back to Listings