Bempedoic Acid Protects Statin-Intolerant Individuals Against Ischemic Events

Bempedoic acid provides effective protection against ischemic stroke for patients who cannot tolerate statins, according to a recent analysis from the CLEAR Outcomes trial, a study enrolling nearly 14,000 statin-intolerant patients with significant cardiovascular risk. 

A prespecified analysis of the Cholesterol Lowering via Bempedoic Acid, an ATP Citrate Lyase (ACL)–Inhibiting Regimen (CLEAR) Outcomes trial showed that patients with high cardiovascular risk and intolerance to statin therapy experienced significant reductions in low-density lipoprotein cholesterol (LDL-C) levels, which reduced the risk for cardiovascular events by 13% in this population (Nicholls SJ et al. JAMA Cardiol 2024; 9:245–253). About half of the study population was assigned to receive bempedoic acid (180 mg daily), while the other half was randomized to placebo. Data collected over a median follow-up period of 3.4 years showed that treatment with bempedoic acid decreased the total burden of cardiovascular events, including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and coronary revascularization. However, the effects of bempedoic acid on the risk for stroke, including hemorrhagic and ischemic events, did not reach statistical significance in the initial analysis. These findings were in line with results from randomized clinical trials investigating other lipid-lowering therapies, such as ezetimibe, which also showed that treatment had no effects on overall stroke reduction. 

The post-hoc analysis presented at the 75th Annual Scientific Session of the American College of Cardiology, in New Orleans, showed a 22% reduction in ischemic stroke risk, with more prominent protective effects seen in participants without prior stroke. Nearly 300 participants had at least one fatal or non-fatal stroke during the analyzed study period. Approximately 12% of the participants in CLEAR Outcomes had a history of stroke. Those participants were less likely to be current smokers and had a higher prevalence of atrial fibrillation. While the protective effect was limited to ischemic stroke, presenting author Carolina Zingano, MD, an internal medicine resident at the Cleveland Clinic, in Cleveland, Ohio, noted that the number of hemorrhagic stroke events in the trial was too low for any conclusions.   

While lipid-lowering medications have long been a cornerstone of stroke prevention, non-statin therapies such as bempedoic acid may boost cardiovascular protection for people at high risk who cannot take statins, giving clinicians more options for earlier and more aggressive interventions.