Effect of evolocumab on carotid plaque composition in asymptomatic carotid artery stenosis (EVOCAR-1) using magnetic resonance imaging

Background and Aims

To determine the effect of evolocumab treatment in patients with asymptomatic carotid artery stenosis ≥50% on carotid plaque morphology and composition, as determined by magnetic resonance imaging.

Methods

We conducted a double-blind randomized controlled trial in patients with asymptomatic carotid artery plaque with ≥50% stenosis and low-density lipoprotein-associated cholesterol (LDL-C) ≥1.8 mmol/L, despite standard lipid-lowering therapy, with 12 months of evolocumab or placebo injection every two weeks. The primary endpoint was the between group difference in the absolute change from baseline in carotid plaque lipid-rich necrotic core (LRNC), assessed by carotid magnetic resonance.

Results

Due to interrupted recruitment during the COVID-19 pandemic, 33 patients (36% female) were randomised, which was less than the target of 52. Mean age was 68.7 years (SD, 8.5) and baseline LDL-C 2.4 mmol/L (SD, 0.7). LDL-C was reduced with evolocumab to 0.8 mmol/L (SD, 0.5) vs 2.2 mmol/L (SD, 0.7) with placebo at 3 months (between group absolute difference -1.3 mmol/L [95% confidence interval [CI], -1.7 to -0.9], p < 0.001). Evolocumab treatment was associated with a favourable change in LRNC at 12 months of -16 mm³ (SD, 54) whereas the placebo group showed -4 mm³ (SD, 44). Between group differences did not show statistical significance with a placebo-adjusted LRNC change of -17 mm³ ([95% CI, -45 to 12], p = 0.25). Percentage carotid plaque LRNC also numerically reduced at 12 months, however this did not reach statistical significance (-2.4% vessel wall volume [95% CI, -5.7 to 0.9], p = 0.16).

Conclusion

Intensive LDL-C lowering with the addition of evolocumab to maximally tolerated lipid-lowering therapy did not lead to a statistically significant change in vulnerable plaque phenotype characteristics in patients with asymptomatic carotid artery stenosis, but the study was underpowered due to under-recruitment in the context of the COVID-19 pandemic.