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) on maximally tolerated statins. This was the main conclusion from the YELLOW III study. The results further support aggressive lipid lowering in this population.

Despite high-intensity statin therapy, patients with coronary artery disease (CAD) have a considerable residual risk for cardiovascular events. PCSK9 inhibitors have been shown to reduce this residual risk, said Annapoorna Kini, MD, NY, USA), who presented the phase 4 YELLOW III (NCT04710368) results at the American College of Cardiology 2023 Annual Scientific Sessions.¹ Previous studies from her group have shown reduced maxLCBI_4mm (YELLOW I) and increased fibrous cap thickness (FCT) (YELLOW II) in obstructive lesions of patients with CAD after rosuvastatin 40 mg therapy for 6–12 weeks (MaxLCBI_4mm, maximum lipid core burden index in any 4-mm segment along the coronary artery.)

The YELLOW III 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. Participants had stable CAD and were on maximally tolerated statin therapy. The two primary endpoints were: 1) change in FCT assessed by OCT; and 2) change in maxLCBI_4mm 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 maxLCBI_4mm from 306.8 to 213.1 (absolute change, -93.7; P<0.001). There was also a reduction 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 Dr. Kini. “PBMC transcriptomic data will allow predictive models for detecting subjects who demonstrate the greatest response regarding plaque morphology to PCSK9 inhibition therapy.”

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