Efficacy and safety of bempedoic acid among patients with and without diabetes: prespecified analysis of the CLEAR Outcomes randomised trial.
Level 2 - randomized trial
Prespecified subgroup analysis of a multi-center randomized controlled trial
PubMed 38061370 · doi:10.1016/S2213-8587(23)00316-9
What was done
In a prespecified analysis of the CLEAR Outcomes randomized, double-blind, placebo-controlled trial across 1,250 sites in 32 countries, 13,970 statin-intolerant patients with high cardiovascular risk and LDL cholesterol ≥2.59 mmol/L were randomized (1:1) to receive bempedoic acid 180 mg once daily or placebo. Patients were stratified at baseline by glycemic status into diabetes (n=6,373), prediabetes (n=5,796), and normoglycaemia (n=1,801). The primary efficacy endpoint was a four-component major adverse cardiovascular event (MACE-4: CV death, nonfatal MI, nonfatal stroke, or coronary revascularization) over a median follow-up of 3.4 years. The incidence of new-onset diabetes and changes in HbA1c were evaluated in patients without baseline diabetes.
What was found
Among patients with diabetes, bempedoic acid significantly reduced MACE-4 risk compared to placebo (HR 0.83; 95% CI 0.72–0.95; absolute risk reduction 2.4%), with no evidence of effect modification across glycemic strata (interaction p=0.42). In patients without diabetes at baseline, the incidence of new-onset diabetes was similar between groups: 11.1% (429/3,848) with bempedoic acid versus 11.5% (433/3,749) with placebo (HR 0.95; 95% CI 0.83–1.09). HbA1c levels at month 12 and study end did not differ between treatment arms in prediabetic or normoglycemic participants. Placebo-corrected LDL cholesterol and high-sensitivity C-reactive protein at 6 months were significantly reduced across all glycemic strata (all p<0.001).
Why it matters
Unlike statins, which can elevate glycemia and increase the incidence of new-onset diabetes, bempedoic acid effectively lowers cardiovascular risk and inflammatory markers without adversely impacting glycemic control or increasing diabetes risk.
Limits
The study population was restricted to statin-intolerant individuals at high cardiovascular risk, which may limit generalizability to broader patient groups taking background statin therapy. Specific numerical reductions in LDL-C and hsCRP values were not provided in the abstract.
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