Study Shows Bempedoic Acid Comparable to Statins in Cardiovascular Protection

The cardiovascular benefits of bempedoic acid (Nexletol) can be predicted by the magnitude of change in low-density lipoprotein cholesterol (LDL-C) and are comparable to those achieved with statin therapy, according to a new analysis of the CLEAR Outcomes trial.

Coming just months after receiving a historic approval from the US Food and Drug Administration (FDA) as the first nonstatin LDL-C-lowering agent to receive a primary prevention indication, the new analysis suggests the reduction in cardiovascular risk achieved with bempedoic acid was on par with that of statins when considering an equivalent decrease in LDL-C levels.¹

“The results of this analysis of the CLEAR Outcomes trial reinforce the primary goal of lipid management to achieve optimal LDL-C lowering, rather than focus on the specific class of agents used to do so,” investigators wrote.¹

A novel ATP citrate lays inhibitor from Esperion, the initial approval for bempedoic acid, as monotherapy and in combination with ezetimibe (Nexlizet), came in February 2020 and indicated the agent for lowering LDL-C based on data from the CLEAR program. However, despite the approval and supporting data, many in the field still looked ahead to the results of the then-ongoing cardiovascular outcomes trial—CLEAR Outcomes.^1,2

Presented at ACC.23 and simultaneously published in the New England Journal of Medicine, results of the study, which included 13,970 statin-intolerant patients, suggested risk of a major cardiovascular event was significantly lower with bempedoic acid (11.7%) than with placebo therapy (13.3%) (Hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79 to 0.96; P = .004). Further analysis suggested bempedoic acid was associated with reductions in the incidences of a composite of death from cardiovascular causes, nonfatal stroke, or nonfatal MI (HR, 0.85; 95% CI, 0.76 to 0.96; P = .006), fatal or nonfatal MI (HR, 0.77; 95% CI, 0.66 to 0.91; P = .002), and coronary revascularization (HR, 0.81; 95% CI, 0.72 to 0.92; P = .001).²

On March 22, 2024, the approved label expansions for bempedoic acid and bempedoic acid with ezetimibe to include primary and secondary prevention of cardiovascular risk.²

In the current analysis, a team of investigators led by A. Michael Lincoff, MD, vice chairman of the Robert and Suzanne Tomsich Department of Cardiovascular Medicine at the Cleveland Clinic, sought to estimate whether the magnitude of cardiovasular risk reduction achieved with bempedoic acid was comparable to statin therapy when assessed per standardized unit change in LDL-C. With this in mind, investigators designed their study leveraging methodology of the Cholesterol Treatment Trialists’ Collaboration (CTTC), which defined a major vascular event as a composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal stroke, or coronary revascularization.¹

For the purpose of analysis, investigators estimated HRs for CTTC-defined endpoints of interest normalized to 1 mmol/L differences in LDL-C between the placebo and bempedoic acid groups. Investigators pointed out the normalized HR per 1 mmol/L reduction in LDL-C for stain therapy used for reference in their analyses was derived from a 2010 CTTC meta-analysis.^1,3

Upon analysis, results indicated a CTTC-defined major vascular event occurred among 10.1% of the bempedoic acid group and 11.7% of the placebo group (HR, 0.85; 95% CI, 0.77 to 0.94). When assessing the risk reduction per normalized per 1 mmol/L reduction in LDL-C, the HR for bempedoic acid (0.75; 95% CI, 0.63 to 0.90) was comparable to the rate ratio reported with statin therapy (0.77; 95% CI, 0.76 to 0.80) in the aforementioned meta-analysis. Further analysis revealed this was consistent in primary and secondary prevention subgroups.^1,3

“While statins remain the first-line therapy in cardiovascular disease prevention, treatment with bempedoic acid can provide significant reductions in cardiovascular risk among patients who cannot achieve desired LDL-C levels with statins, including those are unable or unwilling to tolerate guideline-recommended doses of statins or who fail to experience sufficient LDL-C lowering despite intensive statin therapy,” investigators concluded.¹

References:

1. Lincoff AM, Ray KK, Sasiela WJ, et al. Comparative Cardiovascular Benefits of Bempedoic Acid and Statin Drugs. J Am Coll Cardiol. 2024;84(2):152-162. doi:10.1016/j.jacc.2024.04.048
2. Campbell P. Bempedoic acid wins FDA approval for reducing cardiovascular risk in primary, secondary prevention. HCP Live. March 22, 2024. Accessed July 8, 2024. https://www.hcplive.com/view/bempedoic-acid-wins-fda-approval-for-reducing-cardiovascular-risk-reduction-in-primary-secondary-prevention.
3. Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-1681. doi:10.1016/S0140-6736(10)61350-5