Effects of Evolocumab on Coronary Plaque Composition and Microcalcification Activity by Coronary PET and CT Angiography

Abstract

Background: The effects of evolocumab on the underlying coronary disease activity by positron emission tomography (PET) and coronary tree plaque composition by coronary computed tomography angiography (CTA) have not been described.

Objectives: This prospective imaging study aimed to evaluate changes in coronary plaque composition on coronary CTA and coronary microcalcification, a marker of plaque activity, on ¹⁸F-sodium fluoride (NaF) positron emission tomography (PET) after evolocumab treatment.

Methods: This single-arm, prospective, open-label study enrolled patients with baseline extensive noncalcified plaque volume by coronary CTA (>440 µL overall coronary artery or >250 µL in any single plaque). All participants underwent baseline and 18-month follow-up coronary CTA and ¹⁸F-NaF PET. Disease activity was evaluated with ¹⁸F-NaF PET by maximum target-to-background ratios at the lesion level and by coronary microcalcification activity for the entire coronary tree.

Results: A total of 47 patients (age 61.8 ± 10.1 years, 87% male) and 196 lesions were studied. Twenty-three (48.9%) patients were asymptomatic, 16 (34%) presented with chest pain, and 8 (17%) presented with dyspnea. Four (8.5%) patients had a prior coronary artery disease history. At a mean follow-up of 18 months, there was no significant 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). Changes in plaque composition were observed, with 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). In contrast, there was an increase in calcified plaque (108.9 ± 133.7 µL to 148.7 ± 175.3 µL, difference: 39.8 ± 56.1 µL; P < 0.001). There was 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).

Conclusions: In stable patients with extensive noncalcified plaque volume at baseline, 18 months of evolocumab treatment was associated with a shift toward a lower risk quantitative plaque phenotype and reduction in microcalcification activity. (Effect of Evolocumab on Coronary Atherosclerosis; NCT03689946).

Keywords: (18)F-NaF PET; computed tomography angiography; coronary artery disease; evolocumab; plaque.