Small phase 4 trial shows carotid plaque regression after short-term evolocumab treatment

This summary is based on the presentation of C.David Mazer, MD (Toronto, ON, Canada) at the ESC Congress 2024 - Primary Results of SLICE-CEA CardioLink-8: A Randomized Trial of Evolocumab on Carotid Artery Atherosclerotic Plaque Characteristics in People with Asymptomatic High-Risk Carotid Stenosis.

Introduction and methods

Statins reduce carotid plaque vulnerability and risk of ischemic stroke. PCSK9 inhibitors also decrease LDL-c levels and risk of ischemic events, including stroke, in patients with prevalent ASCVD. However, it is not clear whether LDL-c lowering using PCSK9 inhibitors favorably alters plaque characteristics and vulnerability in patients with asymptomatic, severe carotid artery stenosis.

The SLICE-CEA (A Study of Evolocumab on Carotid Artery Atherosclerotic Plaque Morphology Prior to Carotid EndArterectomy) CardioLink-8 trial was a Canadian, multicenter, open-label, blinded-outcome, phase 4 RCT that included 63 patients (aged ≥40 years) with asymptomatic, unilateral, severe (70%–99%) carotid artery stenosis and ≥1 high-risk features (e.g., recent stroke, T2D, renal dysfunction) who were on moderate- to high-intensity statin therapy or had well-documented statin intolerance. Participants were randomized to subcutaneous evolocumab (140 mg every 2 weeks), in addition to current medical treatment, for 26 weeks or usual care.

The primary endpoint was change in lipid-rich necrotic core (LRNC) volume as measured by MRI from baseline to end of treatment. Secondary endpoints were MRI-measured changes in vessel wall and vessel lumen volumes. The researchers used an intent-to-treat analysis including all participants with evaluable MRI scans at baseline and follow-up (evolocumab: n=23; usual care: n=25).

Main results

• At 6 months, the change in LRNC volume from baseline was –8.4 mm3 in patients treated with evolocumab and 64.9 mm3 in those receiving usual care (P=0.017).
• The components of the primary endpoint were vessel wall intraplaque hemorrhage (IPH) volume and vessel wall lipid volume. There were significant differences in the change in these 2 components between the evolocumab and usual-care groups (both P≤0.037), with evolocumab treatment resulting in a marked reduction from baseline in vessel wall lipid volume.
• Subgroup analyses showed the treatment effect of evolocumab versus usual care on the primary endpoint was consistent across subgroups stratified by, for example, sex, age, baseline LDL-c levels, or presence of IPH at baseline (all P for interaction>0.05).
• The secondary endpoints (changes in vessel wall and lumen volumes) did not show statistically significant differences between the treatment groups (both P>0.05).
• Over 6 months, fewer patients in the evolocumab group showed progression of LRNC and vessel wall lipid volumes compared with the usual-care group (both P≤0.013).

Conclusion

This small phase 4 trial showed 6 months of evolocumab treatment led to regression of the LRNC (as measured by MRI) and attenuated disease progression compared with usual care in patients with asymptomatic, severe, high-risk carotid artery stenosis.

- Our reporting is based on the information provided at the ESC Congress 2024 -