Feasibility and efficacy of PCSK9 inhibitors in cases of statin therapy limitation or intolerance

Abstract

Cardiovascular diseases are a common cause of death throughout the world, and in Russia this figure reaches high values as well. The main cause of cardiovascular pathologies is atherosclerosis, which develops against the background of lipid metabolism disorders, in particular, the accumulation of low-density lipoprotein cholesterol. Statins are the main drug in the complex therapy of dyslipidemia, however, their limited use in patients with diagnosed diabetes mellitus and statin intolerance reduces the possibilities and effectiveness of adequate long-term therapy for hyperlipidemia. PCSK9 inhibitors are promising drugs in terms of efficacy, nevertheless, the question of the possibility of using these drugs in patient groups with statin limitations arises. The purpose of the review. This article provides information on the use of PCSK9 inhibitors in the largest populations with limitations to statin therapy (patients with diabetes mellitus and patients with statin intolerance). We identified potentially relevant studies by searching the electronic databases MEDLINE, SCOPUS, PubMed, Google Scholar, and the Cochrane Database of Systematic Reviews over the last 5 years up to March 2023 using the terms: dyslipidemia, hyperlipidemia, atherosclerosis, PCSK9 inhibitor, statins, low-density lipoproteins, cholesterol, efficacy, safety, therapy. Further, according to the inclusion and exclusion criteria, as well as independent selection, all authors of this article selected the sources that met the criteria and compiled this review. Results. PCSK9 inhibitors are generally a safe, well tolerated, and effective therapeutic strategy with an established role in the therapeutic treatment of hyperlipidemias. Theoretically, PCSK9 inhibitors can be used as an alternative to statin therapy for groups of patients with statin intolerance and those with diagnosed diabetes mellitus, as well as in risk groups. As the experience with using PCSK9 inhibitors in the Russian Federation is growing rapidly, future trials are expected to shed light on their long-term safety and tolerability. On the other hand, other potential therapeutic strategies targeting PCSK9 are being developed, including inclisiran, already registered in the Russian Federation, which is also promising in the treatment of lipid metabolism disorders.