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Evolocumab improves coronary plaque morphology in stable CAD

Presented By
Prof. Annapoorna Kini, Icahn School of Medicine at Mount Sinai, NY, USA
ACC 2023

More intensive lipid lowering with the addition of evolocumab for 26 weeks was associated with a significant and substantial benefit on coronary plaque characteristics in patients with coronary artery disease (CAD) receiving maximally tolerated statins. The results of the YELLOW III further support more aggressive lipid lowering in this population.

Despite high-intensity statin therapy, CAD patients still have a considerable residual risk of cardiovascular events. PCSK9 inhibitors have been shown to reduce this residual risk, said Prof. Annapoorna Kini (Icahn School of Medicine at Mount Sinai, NY, USA), who presented the phase 4 YELLOW III (NCT04710368) results [1]. Previous studies from her group have shown reduced maximum lipid core burden index in any 4-mm segment along the coronary artery (maxLCBI4mm; YELLOW I) and increased fibrous cap thickness (FCT) (YELLOW II) in obstructive lesions of CAD patients after rosuvastatin 40 mg therapy for 6–12 weeks [2,3].

The YELLOW III study aimed to assess the effect of 26 weeks of evolocumab (140 mg every 2 weeks) on coronary plaque morphology using optical coherence tomography (OCT) and near-infrared spectroscopy intravascular ultrasound (NIRS/IVUS), as well as peripheral blood mononuclear cell (PBMC) gene expression analysis [1]. The participants had stable CAD and were on maximally tolerated statin therapy. The 2 primary endpoints were the change in FCT assessed by OCT and change in maxLCBI4mm by NIRS.

Of 329 screened patients, 137 were enrolled and 110 completed the 26-week follow-up. The results showed a significant FCT increase measured by OCT from 70.9 to 97.7 (absolute change 26.8; P<0.001). Furthermore, NIRS showed a reduction in maxLCBI4mm from 306.8 to 213.1 (absolute change -93.7; P<0.001). A reduction was also seen in atheroma volume by IVUS in angiographically non-obstructive lesions. The prevalence of thin-cap fibroatheroma (TCFA) lesions was reduced from 48% to 13%. At 6 months follow-up, 20% of patients did not demonstrate FCT thickening, and 24% did not experience LCBI reduction.

“The first multimodality imaging report in stable patients with non-obstructive lesions and lower levels of LDL-C at baseline, compared to previous trials, further supports aggressive lipid lowering in the patient population,” concluded Prof. Kini. “PBMC transcriptomic data will allow predictive models for detecting subjects who demonstrate the greatest response regarding plaque morphology to PCSK9 inhibition therapy.”

  1. Kini AS, et al. Effect of evolocumab on coronary plaque characteristics in stable coronary artery disease: A multimodality imaging study (the YELLOW III study). Session 403-14, ACC Scientific Session 2023, 4–6 March, New Orleans, USA.
  2. Kini AS, et al. J Am Coll Cardiol. 2013;62(1):21–29.
  3. Kini AS, et al. J Am Coll Cardiol. 2017;69(6):628–640.


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