Start the treatment as soon as possible to bring the Ldl cholesterol down to the desired values. Because the lower it is, the better. This objective, valid for the entire population, becomes fundamental for those who deal with atherosclerotic cardiovascular disease. The “bad” cholesterol is in fact a causal factor of the obstruction of the vessels and the consequent ischemia. For those suffering from atherosclerotic cardiovascular disease, therefore it is classified at very high risk, it is necessary to reduce the Ldl values drastically, bringing them below 55 milligrams per deciliter. These declines can be achieved with various strategies, often including PCSK9 inhibitory monoclonal antibodies. For one of these, evolocumab, there are long-term clinical results in terms of safety and tolerability, up to more than eight years, in patients with atherosclerotic cardiovascular disease. The evidence comes from the presentation from the open label extension (Ole) of the phase three Fourier study, presented at the Congress of the European Society of Cardiology (Esc) and published simultaneously on Circulation.
Almost 7,000 patients treated
The Fourier-Ole studies evaluated 6,635 patients from the original study (3,355 initially randomized to take evolocumab and 3,280 to take placebo) in the US and Europe. They were conducted to evaluate the long-term safety and tolerability of the drug in adults with clinically evident atherosclerotic cardiovascular disease. Median monitoring lasted up to 5 years and with a maximum therapy exposure of over eight years. Data analysis showed that evolocumab led to a clinically significant and sustained reduction in LDL cholesterol levels, with 80% of patients achieving levels below 55 milligrams per deciliter. In addition, the 58 percent reduction in baseline LDL cholesterol values was consistent over the long-term follow-up of approximately 5 years. Furthermore, an initial analysis shows a lower rate of major cardiovascular events such as heart attack, stroke or death from such diseases in patients who originally took the drug, compared to those treated with placebo in the original Fourier study 1.
The role of Italy in research
A total of nine Italian centers participated in the Fourier-Ole Study, enrolling a total of 198 patients. “One aspect that emerges from the study is the patients’ total adherence to therapy – he underlines Piera Angelica Merlini of the Department of Cardiology of the Niguarda Hospital in Milan. The total adherence of patients to the therapy is very important because it means that the drug has a good tolerability profile. ” Another fact that emerges is that of the importance of an early start of therapy. “Patients who received active treatment in the first thirty months saw a reduction in cardiovascular events and mortality. This suggests that a timely start of treatment and a prolonged reduction in cholesterol levels allow to obtain a stabilization of the coronary tree – and not only coronary – with a consequent reduction in mortality “. LDL cholesterol is the main modifiable risk factor for the development of cardiovascular disease, yet nearly half of post-heart attack patients do not meet the guideline target of LDL cholesterol levels below 55 milligrams per deciliter, including those who are taking high-intensity statins. And about a third of patients who have suffered an ischemic attack risk another cardiovascular event over the next five years.
An Italian study in real life
In addition to the data from this research, a survey conducted entirely in Italy confirms the possibility of reaching and maintaining target LDL cholesterol levels over time thanks to PCSK9 inhibitors. i is also confirmed by the results of an all-Italian study by Real World Evidence which recruited 798 patients with ischemic cardiovascular disease or with familial hypercholesterolemia who had been on therapy with a PCSK9 inhibitor for at least six months. “Patients had an average reduction in cholesterol levels of 64% which was maintained throughout the 19 months of follow-up. Adherence and persistence to therapy were higher than 95%, with a drug discontinuation rate of 3% – he comments Pasquale Perrone Filardi, author of the study and elected president of the Italian Society of Cardiology “. The study shows that even in a condition in which the patient self-manages the therapy, the results are just as good in terms of high efficacy compared to those of clinical studies, especially in patients with high cardiovascular risk. “As regards adherence to therapy, we know that with other drugs, typically with statins, a large percentage of subjects, up to 50%, abandon therapy one year after the prescription – concludes the expert. Here, on the other hand, we are faced with a class of drugs that show a very high persistence to therapy “. And this, of course, also affects the effectiveness of treatments over time.