Cardiovascular diseases are still today the first cause of death in the world, with an estimated 17.9 million deaths every year. In Italy, cardiovascular diseases are responsible for 35.8% of all deaths (32.5% in men and 38.8% in women), exceeding 230,000 cases per year and in 2017 alone, 47,000 deaths were attributed to hypercholesterolemia. On Thursday 30 March and Friday 31 March the leading experts in Italian Cardiology will meet in Rome at the Auditorium Aurelia Congress Center for ‘Lipids in Rome – Old challenges and new opportunities’ organized by Anmco (the National Association of Hospital Cardiologists), in collaboration with the Italian Society for the study of Atherosclerosis and with the patronage of the American College of Cardiology.
“Fifty years of clinical studies highlight the direct correlation between LLD cholesterol and atherosclerotic cardiovascular disease. Patients are often asymptomatic, therefore unaware of the risk of developing this dangerous condition, and the disease is diagnosed only after a cardiovascular event caused by an excess of ‘bad’ cholesterol in the blood which, adhering to the internal walls of the arteries, leads to the accumulation of fatty deposits (atherosclerotic plaque) and makes it more difficult for the blood to pass – remember the Anmco cardiologists – Ultimately, high levels of LDL cholesterol they progressively damage the arteries and are among the main causes of myocardial infarction and cerebral stroke.Although hypercholesterolemia is recognized as the most easily modifiable cardiovascular risk factor, unfortunately obtaining an effective and sustained reduction over time in LDL cholesterol levels is still a challenge, so much so that 8 patients out of 10 high-risk are unable to reduce it to recommended levels.”
The event in Rome is aimed not only at the cardiological scientific community but also at doctors of various disciplines in which an assessment will be made of the issues relating to the new therapeutic opportunities currently available aimed at reducing global cardiovascular risk. Particular attention will be paid to the clinical pathways for the implementation of therapies for the control of lipid metabolism alterations.
Experts will discuss the role of cholesterol in determining cardiovascular disease and new therapies. “In fact, in addition to monoclonal antibodies, new ‘intelligent’ drugs have recently become available for clinical use, such as bempedoic acid and Inclisiran, which in addition to being characterized by great ease of use, will make it safer and effective therapy, significantly improving the treatment of cholesterol and consequently the cardiovascular risk of patients – recalls the Anmco – In the last 25 years the therapeutic approach to cardiovascular pathologies has been revolutionized by an explosion of new knowledge, resulting from scientific research of molecular biology and clinical studies. And strategies aimed at managing hypercholesterolemia, the main etiopathogenetic factor of atherosclerotic-based cardiovascular disease, are an essential component of cardiovascular prevention”.
“A condition as silent as it is insidious as hypercholesterolemia must be treated in an incisive and early manner – explains Furio Colivicchi – president of Anmco and director of clinical and rehabilitation cardiology at the San Filippo Neri Asl Roma 1 hospital – The need to obtain lower LDL cholesterol levels low, and to counteract the residual risk associated with other atherogenic factors, brings out the need for additional therapeutic interventions.The most recent scientific evidence indicates that a timely start of treatment with anti-Pcsk9 monoclonal antibodies and a prolonged reduction of levels of of LDL cholesterol make it possible to obtain greater protection against future cardiovascular events, without safety problems being highlighted in long-term studies.The development, and subsequent use in clinical practice, of monoclonal antibodies anti-Pcsk9) has supported two important concepts: the first is related to levels of cholesterol supports the ‘lower is better’ paradigm”.
“Clinical studies with Pcsk9 have confirmed a significant reduction in cardiovascular events with the progressive reduction of plasma Ldl cholesterol, with an increasing benefit even with Ldl cholesterol values <30 mg/dl - adds Colivicchi - With the aim of reducing the risk of cardiovascular events, the guidelines of the European Society of Cardiology, updated in 2019, recommend LDL cholesterol levels below 55 mg/dl in patients at the highest risk of cardiovascular disease.Furthermore, in order to achieve the recommended targets, in these patients the same guidelines recommend the use of a combination therapy of several lipid-lowering agents.The second concept is the persistence of a residual, but not negligible, cardiovascular risk, even with low levels of LDL cholesterol.This evidence underlines the need for interventions earlier preventives and, furthermore, brings to light the role of other atherogenic factors, such as tr glycerides, lipoprotein (a), responsible for the transport of cholesterol in the bloodstream, and the inflammatory cascade”.
“Bempedoic acid, on the other hand – underlines Colivicchi – is a new oral treatment, the first of its kind in terms of its mechanism of action, to be taken once a day, which can be associated with other lipid-lowering treatments to further reduce LDL cholesterol levels. It represents an effective tool in the armamentarium, especially for patients at higher cardiovascular risk who have not achieved their therapeutic goals despite ongoing lipid-lowering therapies and for intolerant patients.This drug has the advantage of being able to be associated with any lipid-lowering therapy, to have a good tolerability profile and to be easily accessible since it can be prescribed by both specialists and general practitioners.Furthermore, since the transformation of the prodrug into its active form occurs through an enzyme expressed exclusively in the liver, the bempedoic acid does not inhibit the synthesis of cholesterol at lev muscle and, therefore, has a reduced risk of muscle symptoms compared to statins.”
“Finally, inclisiran – continues Colivicchi – is another innovative drug in its mechanism of action for the reduction of LDL cholesterol as it falls into the class of RNAi (Rna interference) therapeutic agents, drugs that silence messenger RNA (mRna), and represents a new approach to the management of patients with hypercholesterolemia.It is a small double-stranded interfering RNA (siRna) with a high affinity for the liver, within which it reduces the levels of a protein called Pcsk9, involved in the metabolism of cholesterol. This mechanism increases the liver’s ability to absorb LDL cholesterol and consequently leads to a reduction in the levels of bad cholesterol present in the blood. Specifically, inclisiran inhibits the production of Pcsk9, so it acts upstream of the monoclonal antibodies that antagonize the activity of Pcsk9.One of the advantages of Inclisiran treatment is the therapeutic regimen which consists of only two so administrations per year, through a subcutaneous injection. The drug can be prescribed by the specialist and its administration is carried out by a health professional.
“These new therapies – concludes Colivicchi – will help the numerous patients who are not adherent to the prescribed treatments, often precisely due to side effects of the therapies, or who in any case fail to reach the optimal LDL cholesterol targets. Reducing cholesterol means reducing cardiovascular disease and it is therefore essential to change the attitude towards cholesterol treatment to improve global cardiovascular risk”.
