Coronary artery disease occurs when cholesterol deposits build up in the walls of the heart’s arteries, leading to formation of plaques that begin as areas of inflammation. When inflamed plaques grow large, they become prone to rupture, which can cause heart attack. Evolocumab is in a class of drugs called PCSK9 inhibitors that can dramatically reduce cholesterol.

“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 published in JACC: Cardiovascular Imaging.

Investigators administered evolocumab to 47 patients, all of whom had substantial buildup of noncalcified plaque in their coronary arteries. This type of plaque is regarded as higher risk than calcified plaque because it is softer and more likely to rupture and cause harm.

Before and 18 months after treatment with evolocumab, investigators studied inflammation in the coronary arteries using radioactive sodium fluoride and imaging with positron emission tomography (PET). They also used coronary computed tomography angiography (CCTA) coupled with a novel artificial intelligence quantitative method developed at Cedars-Sinai to measure changes in inflammation and plaque volumes in the coronary arteries.

The scans showed that, on average, plaque inflammation decreased and noncalcified plaque became smaller with evolocumab.

“Most attention has been placed on the cholesterol-lowering effects of PCSK9 inhibitors,” said Donghee Han, MD, a Cedars-Sinai internal medicine resident who is also a researcher in Berman’s laboratory and joint 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.”

Other Cedars-Sinai authors include Rebekah Park, Heidi Gransar, Mark Hyun, John D. Friedman, Sean W. Hayes, Louise E. J. Thomson, Alan C. Kwan, Prediman K. Shah, Sarah Wetzel, Chloe Findling, Piotr J. Slomka and Damini Dey. Other authors include joint first author Evangelos Tzolos, Matthew Budoff, Jacek Kwiecinski and co-senior author Balaji K. Tamarappoo.

This study was supported in part by NIH grants 1R01HL148787-01A1 and R35HL161195, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and Amgen Inc.  

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