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The efficacy of bempedoic acid on cardiovascular outcomes is not impacted by autoimmune or inflammatory disease

Bempedoic acid, compared with placebo, reduced the risk of major adverse cardiovascular events among patients with statin intolerance, regardless of the presence of autoimmune or inflammatory disease.

Dr Bernardo Frison Spiazzi (Cleveland Clinic, OH, USA) presented a subanalysis of CLEAR Outcomes (NCT02993406), a randomised, double-blind, placebo-controlled trial that assigned patients intolerant of statins and at high risk for cardiovascular disease to bempedoic acid or placebo [1]. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularisation. In total, 13,970 patients were enrolled, including 1,044 with a history of autoimmune or inflammatory disease at baseline.

Bempedoic acid versus placebo led to similar improvements in the primary endpoint among patients with a history of autoimmune or inflammatory disease (HR 0.89; 95% CI 0.65–1.21) and those without such a history (HR 0.87; 95% CI 0.79–0.96). Comparable effects were observed across secondary endpoints, including the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, as well as individual endpoints such as fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, and coronary revascularisation.

In addition, bempedoic acid significantly reduced low-density lipoprotein cholesterol (LDL-C) from baseline to month 6 in both patients with autoimmune or inflammatory disease (-23.8% vs -0.5% with placebo) and those without such conditions (-21.5% vs -0.6% with placebo).

Overall, Dr Spiazzi concluded that, in the CLEAR Outcomes trial, “bempedoic acid demonstrates a consistent efficacy profile in lowering LDL-C and major adverse cardiovascular events in participants with and without autoimmune inflammatory disease.”

  1. Spiazzi BF, et al. Bempedoic acid and cardiovascular outcomes in patients with autoimmune or inflammatory diseases: An analysis of the CLEAR Outcomes trial. ACC 2026, 28–30 March, New Orleans, LA, USA.

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Evolocumab improves cardiovascular outcomes in patients with high-risk diabetes without significant atherosclerosis

Evolocumab versus placebo significantly improved outcomes for coronary heart disease death, myocardial infarction, and ischaemic stroke in patients with high-risk diabetes and no significant atherosclerosis.

Prof. Nicholas Marston (Harvard Medical School, MA, USA) presented data from VESALIUS-CV (NCT03872401), a phase 3, randomised 1:1, controlled trial evaluating evolocumab versus placebo on background of statin therapy in stable patients at high risk of cardiovascular events but without prior myocardial infarction or stroke. Patients were eligible if they had qualifying atherosclerotic risk factors and/or high-risk diabetes. The dual primary endpoints were 3-point major adverse cardiovascular events (MACE; time to coronary heart disease death, myocardial infarction, or ischaemic stroke) and 4-point MACE (3-point MACE plus ischaemia-driven arterial revascularisation). The presented analysis focused on patients with no significant atherosclerosis (n=3,655) and high-risk diabetes [1].

In this subgroup, evolocumab significantly prolonged the time to 3-point MACE compared with placebo, corresponding to a 31% relative risk reduction and a 2.1% absolute reduction. Evolocumab also significantly reduced 4-point MACE (absolute risk reduction, 2.9%; HR 0.69; 95% CI 0.55-0.86; P=0.001). The benefit of evolocumab was maintained for cardiovascular death (cumulative incidence 2.6% vs 4.0% at 5 years) and all-cause mortality (cumulative incidence 7.8% vs 10.1% at 5 years) [1]. The incidence of adverse events was similar between treatment groups [2].

In summary, VESALIUS-CV demonstrated significant reductions in MACE among high-risk primary-prevention patients with diabetes who had no known significant atherosclerosis. “The benefits observed in this subgroup support earlier intensification of lipid-lowering therapy beyond statins in the atherosclerotic cardiovascular disease continuum,” concluded Prof. Marston. “These data further suggest that, even in lower-risk patients, LDL-C targets typically reserved for very high-risk secondary prevention populations may be appropriate” [1].

  1. Marston N, et al. Evolocumab in patients without significant atherosclerosis: Results from VESALIUS-CV. ACC 2026, 28–30 March, New Orleans, LA, USA.
  2. Bohula EA, et al. N Engl J Med. 2026;394(2):117-127.

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Therapy targeting lower LDL-C levels improves cardiovascular outcomes

Targeting low-density lipoprotein cholesterol (LDL-C) levels <55 mg/dL is associated with improved cardiovascular outcomes compared with a target of <70 mg/dL in patients with atherosclerotic cardiovascular disease, without an increase in adverse events, according to a report by Prof. Byeong-Keuk Kim (Yonsei University College of Medicine, Republic of Korea) [1].

Ez-PAVE (NCT04626973) was a phase 3, randomised, investigator-led trial conducted entirely in Korea. Patients with atherosclerotic cardiovascular disease were assigned to either an intensive LDL-C target (<55 mg/dL) or a conventional target (<70 mg/dL). Within these groups, patients were further randomised to receive either a statin plus ezetimibe combination or a statin monotherapy. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, any revascularisation, or hospitalisation for unstable angina. In total, 3,048 patients were randomised and included.

In Ez-PAVE, intensive LDL-C targeting resulted in significantly lower rates of the primary endpoint compared with conventional targeting, corresponding to a 33% reduction in relative risk. Analyses of individual components showed no significant differences in cardiovascular death or all-cause mortality, but significantly lower rates of non-fatal myocardial infarction, non-fatal stroke, and revascularisation with intensive targeting. Safety analyses demonstrated no significant differences between groups in new-onset diabetes, worsening of glycaemic control, statin-associated muscle symptoms, new cancer diagnoses, or elevations in aminotransferases or creatine kinase. Notably, intensive targeting was associated with significantly lower rates of creatinine elevation to >1.5 times baseline.

“Ez-PAVE is the first randomised trial comparing LDL-C targets of <55 mg/dL versus <70mg/dL in patients with atherosclerotic cardiovascular disease,” concluded Prof. Kim. “Intensive targeting was associated with a significantly lower 3-year risk of the composite endpoint than conventional targeting, without major safety concerns. These findings provide randomised evidence supporting more intensive lipid-lowering strategies for secondary prevention, consistent with guideline recommendations.”

  1. Kim K, et al. Intensive low-density lipoprotein cholesterol targeting in patients with atherosclerotic cardiovascular disease. ACC 2026, 28–30 March, New Orleans, LA, USA.

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