THE NEW PCSK9-INHIBITOR INCLISIRAN: AN EXCEPTIONAL REDUCTION IN LDL CHOLESTEROL FROM THE FIRST PATIENTS OF THE NIGUARDA HOSPITAL

Abstract

Objective: Dyslipidemia is one of the most prominent risk factors in coronary artery disease. With the new strict target of Low Density Lipoprotein (LDL) cholesterol in secondary prevention in some patients oral medication may not be sufficient. Inclisiran is a small interfiring RNA that inhibits the hepatic PCSK-9 synthesis inducing a reduction in low-density lipoprotein levels up to 50%. Conveniently, it only requires one administration every six months. Design and method: A 53-year-old man, with no previous cardiologic history, presented to our emergency department reporting acute chest pain and left arm paresthesia developed after an emotional stress. Electrocardiogram was normal with a slightly and stable increased of high sensitivity troponin T levels (18 ng/l). The patient had the following cardiovascular risk factors: type 2 diabetes mellitus, dyslipidemia, obstructive sleep apnea syndrome, obesity (body mass index 30), sedentary lifestyle. Taking into consideration his clinical presentation and his cardiovascular risk, a coronary computer tomography was performed showing severe stenosis in Left Anterior Descending (LAD) and right coronary arteries. The subsequent coronary angiography confirms the severe stenosis in the proxymal LAD and the mild stenosis (30%) in the right coronary artery. The LAD was treated with a drug eluting stent. At the time of the event the patient was already on therapy with rosuvastatina/ezetimibe 10/10 mg that we increased to a dosage of 20/10 mg. At the first medical examination after the hospitalization, his blood tests showed uncontrolled LDL cholesterol (70 mg/dl). We therefore decided to try lowering his cholesterol levels with addition of inclisiran. Results: After 3 months of inclisiran therapy, his blood test showed a surprisingly decrease in cholesterol levels (total cholesterol 78 mg/dl and LDL 11 mg/dl) reaching the desirable target. Conclusions: Inclisiran is a valid therapeutic strategy for reaching the desiderable cholesterol target in patient at high cardiovascular risk. In our first patients inclisiran, added to statin and ezetimibe therapy, successfully lowered LDL to the desirable target. Surprinsigly, it lowered LDL up to 85%, much more than expected. Further studies will be needed to identify which patients may be super responders to Inclisiran.