YELLOW III Study Improves Understanding of Evolocumab in CAD Treatment

Annapoorna S. Kini, MD

Credit: Mount Sinai

More intensive lipid lowering with the addition of evolocumab for 26 weeks was associated with significant and substantial benefit on coronary plaque characteristics in patients with coronary artery disease (CAD) on maximally tolerated statins.¹

The results from the YELLOW III Study was presented at the American College of Cardiology (ACC) 2023 Annual Scientific Sessions in New Orleans, Louisiana.

A considerable residual risk of cardiovascular events remains in patients with CAD despite high-intensity statin therapy. PCSK9 inhibitors have reduced this residual risk. Prior results from the investigative team have shown reduced maxLCBI4 mm (YELLOW I) and increased FCT (YELLOW II) in obstructive lesions of patients with CAD after rosuvastatin 40 mg for 6-12 weeks.

The YELLOW III Study aimed to assess the effect of 26 weeks of evolocumab on coronary plaque morphology using intravascular imaging and PMBC gene expression analysis in patients with stable CAD on maximally tolerated statin therapy.

A total of 329 patients were screened for enrollment and 192 were excluded due to criteria including LDL-C criteria not met and no suitable lesion observed on angiography. Of the 137 patients enrolled, 110 completed the 26-week follow-up.

Data showed a significant and substantial increase in the minimum fibrous cap thickness (FCT) by optical coherence tomography (OCT), reduction in lipid core burden index at the maximal 4-mm segment (maxLCBI4mm) by near-infrared spectroscopy, and reduction in atheroma volume by intravascular ultrasound in angiographically non-obstructive lesions.

Study results indicate the prevalence of high-risk vulnerable thin-cap fibroatheroma (TCFA) lesions was reduced from 48% to 13%. 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 supported aggressive lipid lowering in the patient population.

“At 6-month follow-up, 20% of patients did not demonstrate FTA thickening and 24% of subjects did not experience Lipid Core Burden Index reduction,” wrote the investigative team. “Peripheral blood mononuclear cells transcriptomic data will allow predictive models for detecting subjects who demonstrate the greatest response regarding plaque morphology to PCSK9 inhibition therapy.”

With an interest in learning more, the HCPLive editorial team sat down at ACC 2023 with presenting author Annapoorna S. Kini, MD, Interventional Director of Structural Heart Program at Mount Sinai Hospital.

Here is the video of our discussion with Kini:

References

1. Kini A.S. Effect of Evolocumab on Coronary Plaque Characteristics in Stable Coronary Artery Disease: a Multimodality Imaging Study (The YELLOW III Study). American College of Cardiology (ACC) 2023 Annual Scientific Sessions. In: New Orleans, Louisiana.

Disclosures: Kini reports having received funds for consulting or research grants from Abbott Vascular Inc. and Amgen.