Evolocumab May Shift Plaque Profile Toward Lower Cardiovascular Risk

Evolocumab may help reshape high-risk plaque in the arteries, with the drug reducing microcalcification activity and shifting plaque toward a lower-risk profile over 18 months in patients with extensive noncalcified plaque at baseline in a new study.1

Evolocumab, a human monoclonal antibody targeting PCSK9, was first approved by the US Food and Drug Administration (FDA) in August 2015 to lower low-density lipoprotein cholesterol (LDL-C) in patients needing additional reduction. In December 2017, it became the first PCSK9 inhibitor approved to prevent heart attack, stroke, and coronary revascularization in adults with established CVD.

“This discovery has important implications for understanding how evolocumab improves cardiovascular outcomes,” said Daniel S. Berman, MD, director of cardiac imaging in the department of cardiology in the Smidt Heart Institute at Cedars-Sinai and principal investigator of the study.

Berman and colleagues highlighted the lack of evidence on the impact of evolocumab on underlying coronary disease activity by positron emission tomography (PET) and coronary tree plaque composition by coronary computed tomography angiography (CTA). For this imaging study, the team measured the change in coronary plaque composition on coronary CTA and coronary microcalcification on F-sodium fluoride (NaF) PET after evolocumab.

A single-arm, prospective, open-label study, investigators enrolled patients with >440 µL overall coronary artery or >250 µL in any single plaque, who underwent baseline and 18-month follow-up coronary CTA and F-NaF PET. The team determined disease activity by maximum target-to-background ratios at the lesion level and by coronary microcalcification activity for the entire coronary tree.

Overall, 47 patients, with a mean age of 61.8 years and 87% male, with 196 lesions, were included in the study. Among this population, 23 (48.9%) were asymptomatic, 16 (34%) presented with chest pain, and 8 (17%) presented with dyspnea, while 4 (8.5%) had a prior coronary artery disease history.

Across a mean of 18 months, Berman and colleagues identified no notable change in total plaque volume (716.2 ± 431.4 µL to 710.8 ± 456.2 µL; difference, 5.4 ± 97.4 µL; P = 0.705). The investigative team identified changes in plaque composition, including a significant reduction in noncalcified plaque (607.3 ± 346.8 µL to 562.1 ± 337.3 µL, difference: 45.2 ± 63.8 µL; P < 0.001) and low-attenuation noncalcified plaque (37.1 ± 28.9 µL to 20.4 ± 15.4 µL, difference: 16.6 ± 23.5 µL; P < 0.001).

On the other hand, the analysis identified an increase in calcified plaque over 18 months (108.9 ± 133.7 µL to 148.7 ± 175.3 µL, difference: 39.8 ± 56.1 µL; P < 0.001). Further analysis revealed a significant reduction in coronary microcalcification activity (1.35 ± 1.68 to 1.08 ± 1.37; P = 0.004) and lesion target-to-background ratio (1.73 ± 0.85 to 1.62 ± 0.83; P = 0.005).

“Most attention has been placed on the cholesterol-lowering effect of PCSK9 inhibitors,” said Donghee Han, MD, an internal medicine resident at Cedars-Sinai Medical Center and co-first author of the study. “Our findings demonstrate that reducing inflammation may be an important mechanism for reducing the risk of heart attack with these powerful drugs.”

References

1. Han D, Tzolos E, Park R, et al. Effects of Evolocumab on Coronary Plaque Composition and Microcalcification Activity by Coronary PET and CT Angiography. JACC Cardiovasc Imaging. 2025;18(5):589-599. doi:10.1016/j.jcmg.2025.01.005

2. FDA approves Amgen’s new cholesterol-lowering medication RepathaTM (evolocumab). Amgen. August 27, 2025. Accessed May 8, 2025. https://www.amgen.com/newsroom/press-releases/2015/08/fda-approves-amgens-new-cholesterollowering-medication-repatha-evolocumab.

3. FDA approves Amgen’s Repatha® (evolocumab) to prevent heart attack and stroke. Amgen. December 1, 2025. Accessed May 8, 2025. https://www.amgen.com/newsroom/press-releases/2017/12/fda-approves-amgens-repatha-evolocumab-to-prevent-heart-attack-and-stroke.

4. Cedars-Sinai. Research: How cholesterol drug may prevent heart attacks. Newswise. May 5, 2025. Accessed May 8, 2025. https://www.newswise.com/articles/research-how-cholesterol-drug-may-prevent-heart-attacks.