CARotid plaqUe StabilizatiOn and regression with evolocumab: the CARUSO Study

BackgroundEvolocumab promotes coronary plaque regression in patients with coronary artery disease, but little is known regarding carotid plaques (CP). This study aimed to evaluate the impact of evolocumab on top of lipid-lowering therapy (ELLT) on carotid morphological stabilization (MS) and plaque regression (PR) compared to lipid-lowering therapy (LLT) alone. MethodsAsymptomatic patients with internal carotid stenosis[≥]50% and LDL-C[≥]100 mg/dL were randomized to ELLT or LLT and monitored by serial duplex ultrasound. The primary endpoint was a composite of 6-month-MS (i.e., switch from morphologic types I-II to III-IV) and/or 12-month-PR (i.e., reduction of carotid stenosis by at least 5% compared to baseline). The secondary endpoint was LDL-C change at 12 months. Major adverse vascular events (MAVE, i.e., cardiac death, stroke, myocardial infarction, carotid or coronary or peripheral revascularization) were recorded. ResultsA total of 170 patients were randomized. Mean carotid stenosis was 57%. At 6 months, MS occurred in the ELLT group (10.3%) only (p=0.29). At 12 months, PR was numerically more frequent in the ELLT group, without reaching statistical significance (43% versus 35.1%, p=0.42). The primary endpoint was met in 44.3% versus 35.1% (p=0.26). As compared to baseline, 6 and 12-month shifts from low to high-risk types were significantly higher in the LLT group (p=0.03). The 12-month LDL-C percentage reduction was -73.5% with ELLT, and -48.3% with LLT (p=0.0001). At 1 year, MAVE were significantly more frequent with LLT (14.6% versus 2.4%, p=0.005), and the absence of evolocumab was the only predictor (OR 7, p=0.014). ConclusionsIn patients with CP[≥]50% and LDL-C[≥]100 mg/dL, ELLT compared to LLT was associated with numerically but not statistically higher 6-month MS and/or 12-month PR. In the LLT group, 6- and 12-month changes from low to high-risk types, LDL-C, and MAVE were significantly higher. According to these results, evolocumab should be considered standard treatment for patients with CP[≥]50%. The study was registered at www.clinicaltrials.gov (NCT04730973) and Eudract (2020-005663-31). SHORT ABSTRACTPatients with carotid stenosis[≥]50% and LDL-C[≥]100 mg/dL were randomized to evolocumab on top of optimal lipid-lowering therapy (ELLT) or optimal lipid-lowering therapy (LLT) alone to assess the impact of ELLT on carotid plaque morphological stabilization (MS) and plaque regression (PR). At 6 and 12 months, MS and PR occurred in both groups, but were numerically higher in the ELLT group, without reaching statistical significance. In the LLT group, 6- and 12-month changes from low to high-risk types were significantly higher, and the rate of adverse vascular events was sevenfold higher. Evolocumab might become the standard treatment for patients with carotid artery stenosis [≥]50%. CLINICAL PERSPECTIVEO_ST_ABSWhat is new?C_ST_ABSO_LIThe CARUSO is the largest randomized trial evaluating the impact of evolocumab on top of lipid-lowering therapy (ELLT) on carotid morphological stabilization (MS) and plaque regression (PR) monitored by serial duplex ultrasound. C_LIO_LIThe primary endpoint was a composite of 6-month-MS (i.e., switch from morphologic types I-II to III-IV) and/or 12-month-PR (i.e., reduction of carotid stenosis by at least 5% compared to baseline) and was numerically higher in the ELLT group compared to lipid-lowering therapy (LLT) alone, without reaching statistical significance. C_LIO_LIThe 1-year rate of major adverse vascular events (MAVE) was sevenfold higher in the LLT group. C_LI What are the clinical implications?O_LICarotid plaque morphology is a dynamic event, and 6 and 12-month shifts from low to high-risk morphological types were significantly higher in the LLT group, thus suggesting that evolocumab added to LLT may prevent morphological deterioration. C_LIO_LIThe absence of evolocumab was the only independent predictor of MAVE; according to our results, ELLT might become the standard treatment for patients with carotid plaques [≥]50% and LDL-C not at target. C_LIO_LIFuture larger studies are warranted to validate our findings, assess long-term adherence to therapy, and identify subgroups with higher probability of achieving MS and PR. C_LI