Bempedoic Acid Improved Cardiovascular Outcomes in People with Chronic Inflammation

Individuals with autoimmune and inflammatory diseases can benefit from the cardioprotective effects of bempedoic acid, according to a secondary analysis from the CLEAR Outcomes trial. The analysis presented at the 75th Annual Scientific Session of the American College of Cardiology, in New Orleans, provided a close look at inflammation, cholesterol levels, and cardiovascular outcomes in relation to the absence or presence of underlying inflammation associated with certain chronic diseases.  

Patients with autoimmune or inflammatory diseases have an elevated risk for major adverse cardiovascular events (MACE). However, results from previous trials investigating lipid-lowering therapies have sent mixed messages for this subpopulation. More recently, a sub-analysis from the FOURIER trial suggested that intensive lipid-lowering may be especially cardioprotective for people with chronic inflammation (Zimerman A et al. Circulation 2025; 151: 1467-76). The results showed that patients with a history of autoimmune or inflammatory diseases experienced a greater relative risk reduction in MACE when treated with the Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab compared to those without such conditions. 

In the Cholesterol Lowering via Bempedoic Acid, an ATP Citrate Lyase (ACL)–Inhibiting Regimen (CLEAR) Outcomes trial, statin-intolerant patients who were at high risk for or had established atherosclerotic cardiovascular disease were randomized to receive either bempedoic acid (180 mg daily) or placebo and were monitored for a median period of 40.6 months. 

Approximately 1,000 patients (7.5% of the study population) had a history of autoimmune or inflammatory disease, most commonly Hashimoto’s thyroiditis (23%), psoriasis or psoriatic arthritis (23%), and rheumatoid arthritis (19%). Those with autoimmune or inflammatory diseases were predominantly female (60%) and were slightly older (median age of 68 years vs 66 years) than the participants without autoimmune or inflammatory disorders. This sub-population also had a higher prevalence of chronic kidney disease and higher baseline levels of low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP). 

In the post-hoc analysis, the researchers compared the efficacy of bempedoic acid to placebo and analyzed the time to cardiovascular outcomes according to the presence or absence of autoimmune or inflammatory disease. The results showed that baseline autoimmune or inflammatory disease made no difference with respect to cardiovascular outcomes and death rates in the treatment group. The reductions in MACE achieved with bempedoic acid were comparable between participants with and those without autoimmune and inflammatory diseases. MACE included fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, and coronary revascularization. Relative reductions in LDL-C levels and hsCRP levels were also similar between the two groups. 

“The central message of this analysis is that bempedoic acid demonstrates a similar efficacy profile in lowering LDL cholesterol, high-sensitivity C-reactive protein, and major adverse cardiovascular events, independent of baseline presence or absence of autoimmune or inflammatory disease,” said presenting author Bernardo Spiazzi, MD, a resident at the Cleveland Clinic in Cleveland, Ohio. Spiazzi noted that more data are needed to determine whether people with autoimmune and inflammatory diseases have a higher prevalence of statin intolerance. Nevertheless, this vulnerable population, which had higher rates of death and cardiovascular events in the CLEAR Outcomes study, could benefit from novel therapies that can make a dent in the levels of atherogenic lipoproteins and chronic inflammation. 

While clinicians should consider any potential interactions with immunosuppressive therapies, bempedoic acid may have a synergistic effect in this population due to its own anti-inflammatory properties.