I'm Tiziana Aranzulla from the Mauriziano Hospital. We are going to discuss the Caruso study.

What is the current research landscape for evolocumab, and what is the importance behind the trial?
We know that evolocumab is associated with favorable outcomes in patients with coronary artery disease, but, little is known regarding carotid artery disease. We know that evolocumab promotes coronary plaque regression, but we don't know the true impact on carotid plaques. Indeed, only a few case reports and small randomized trials are available. And this is the background of the Caruso study which aimed to evaluate the impact of eboloquumab on top of optimal lipid lowering therapy as compared to lipid lowering therapy alone, on morphological stabilization and carotid plaque regression, to see if we can find the same results as in the coronary landscape.

What was the study design and patient population?
So we randomized patients with carotid artery stenosis more than 50% to optimal lipid lowering therapy alone or to evolocumab on top of optimal lipid lowering therapy. What is important is that we upgraded the lipid lowering therapy to rosuvastatin 20 ezetimibe 10 milligrams in all the patients. And on the same background we put in the evolocumab arm also evolocumab on top of this optimal lipid lowering therapy. We enrolled 170 patients after randomization. 5 withdrew consent before receiving any therapy and, and therefore the Study analysis included 165 patients with 175 carotid plaques. And we followed all these patients with carotid duplex ultrasound at 6 and 12 months. In order to evaluate the impact on the primary endpoint that was morphological stabilization at 6 months and or plaque regression at 12 months. Morphological stabilization was defined as the shift from high risk morphological time types that are carotid plaques with high percentage of hypoechoic areas. And low risk carotid plaques are those with or uniformly echogenic plaque or less than 50% hippoechoic areas. Carotid plaque regression was defined as the reduction by at least 5% in the percentage of carotid stenosis and or reduction of peak systolic velocity by at least 5%.

What were the key findings?
Key findings are three types of findings. The primary endpoint was achieved numerically in a higher rate in the evolocumab arm as compared to the statin arm. But what is very important is that evolocumab reduced morphological deterioration that is the shift, the opposite shift from low risk types to high risk types. So while it promotes a numerically higher rate of morphological stabilization, it also halved the morphological deterioration. This is very important for our patients. Secondary endpoint was LDLc, absolute percentage reduction. And it was achieved significantly, in a significantly higher rate in the evolocomab arm. But what was very important and was a striking result and that is that evolocumab reduced adverse vascular events by sevenfold, at one year. And this is very important because evolocumab was the only independent predictor. The absence of evolocumab was the only independent predictor of adverse vascular events with a number needed to treat to prevent one event of only eight. This is a striking result and it can change the management of patients, with carotid artery disease. Because, according to these findings, evolucumab should become the standard therapy irrespectively regardless of the morphological type. Because what we saw is that also benign, let's call them benign, morphological types at enrollment can shift to high risk, types and the evolocumab prevents this shift.

What are the take-home messages for practice?
First take home message is to, to improve awareness in this patient cohort that is at ultra high risk. So we found that at enrollment only 29% of patients were on full dose statins. That is confirms the severe undertreatment of these patients despite the guidelines recommendation. Plus, if you add evolocumab to optimal lipid lowering therapy, you can reduce by sevenfold your adverse vascular events at one year. So this is a very important message for all the interventionalist and non interventionalist community because can help to prevent many events and also to keep in mind that these patients have a very high risk and guideline recommendations are clear. But clinical practice nowadays it's not in line with the guidelines recommendation first to have larger studies, because although the caruso studies is the largest so far, the numbers are still low.

What further research is needed in this area?
So I would like to see larger studies on this topic and also larger studies may be focused only of our patients who already had an event in their past or without any other cardiovascular risk factor in order to give us other clues to implement our therapy.