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Comparative CV Benefits of Bempedoic Acid and Statin Drugs
Quick Takes
- The Cholesterol Treatment Trialists’ Collaboration reported that whether high- or low-intensity statin treatment, every 1 mmol/L (38.7 mg/dL) reduction in LDL-C over 1 year was associated with a 22% reduction in major vascular events. The findings were comparable with trials of ezetimibe and PCSK9 inhibitors.
- In the CLEAR Outcomes trial of the nonstatin bempedoic acid vs. placebo, normalized per 1 mmol/L reduction in LDL-C, the hazard ratio was 0.75 for bempedoic acid, comparable to the risk ratio of 0.78 for statins.
Study Questions:
Does the relationship between low-density lipoprotein cholesterol (LDL-C) lowering and cardiovascular (CV) benefit achieved with bempedoic acid resemble that observed with statins when standardized per unit change in LDL-C?
Methods:
The study was conducted in the CLEAR Outcomes trial; a randomized placebo-controlled study in 13,970 persons that included primary and secondary prevention in men and women aged 18-85 years with baseline LDL-C of ≥100 mg/dL and unwilling or unable to receive statins. The primary efficacy endpoint was that of the Cholesterol Treatment Trialists’ Collaboration (CTTC), a four-component major adverse coronary event (MACE) composite of death from CV cause, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization in a time-to-first-event analysis. Key secondary endpoints were a three-component MACE composite of death from CV causes, nonfatal MI or nonfatal stroke; fatal or nonfatal MI; coronary revascularization; fatal or nonfatal stroke; death from CV causes; and death from any cause.
To permit indirect comparison of treatment effect of bempedoic acid with statins, the authors used the CTTC statin meta-analysis method of comparing the rate ratio of first event rates between placebo and controlled randomized groups weighted per 1.0 mmol/L absolute difference in LDL-C at 1 year after randomization.
Results:
A first major event occurred in 10.1% of patients in the bempedoic acid group and 11.7% of placebo groups (hazard ratio [HR], 0.85; 95% confidence interval [CI], 077-94). When normalized per 1 mmol/L reduction in LDL-C, the HR was 0.75 (95% CI, 0.63-0.90) comparable to the rate ratio of 0.78 reported for statins in the CTTC meta-analysis. Normalized risk reductions were similar for bempedoic acid and statins for the endpoints of major coronary events, nonfatal MI, and coronary revascularization.
Conclusions:
The investigators conclude that CV risk reduction with bempedoic acid is like that achieved with statins for a given absolute magnitude of LDL-C lowering.
Perspective:
While the benefit of LDL-C lowering for reducing MACE is comparable between bempedoic acid and statins, in the CLEAR trial, bempedoic acid reduced median high-sensitivity C-reactive protein (hsCRP) by 21.6% and mean LDL-C levels by 21.1% at 6 months. The relative efficacy of bempedoic acid compared to placebo was of similar magnitude across baseline subgroups by either hsCRP or LDL-C (Ridker PM, et al., Circulation 2024;149:28-35), implying it is an excellent alternative to statins in primary and secondary prevention for the statin intolerant. It also may have greater benefit than treatments with less or no impact on hsCRP, particularly considering there is no additional cost for bempedoic acid + ezetimibe, which lowers LDL-C by an additional 18%. In contrast to statins, bempedoic acid has no negative effect on glycemic control and does not enter myocytes. The most important side effects at a mean of 3.4 years are an increase in uric acid and a 1% increase in gout.
Clinical Topics: Dyslipidemia, Lipid Metabolism, Nonstatins, Prevention
Keywords: Cholesterol, LDL, Statins
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