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

ESC 2024 – In SLICE-CEA CardioLink-8, evolocumab for 6 months led to regression of the lipid-rich necrotic core and attenuated disease progression compared with usual care in patients with asymptomatic, severe carotid artery stenosis.

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 -