Safety of significant, long-term lipid lowering therapy. Focus on inclisiran, with Braunwald's vision

High blood cholesterol is one of the most important risk factors of atherosclerosis. Currently, four groups of drugs (statins, ezetimibe, PCSK9 inhibitors and bempedoic acid) have large clinical trials proving that the frequency of cardiovascular events can be significantly improved by lowering LDL-cholesterol (LDL-C). According to the lipid guidelines, the reduction of LDL-C should begin as early as possible and should be done as lower as possible for a long term. It should also be borne in mind that the greater the risk, the greater the cardiovascular benefit. Taking this into account, using the new domestic health insurance regulations, we should pay great attention to starting PCSK9 inhibitor treatment as soon as possible in our very high-risk patients, if high-intensity statin and ezetimibe combination therapy is not sufficient. Currently, evolocumab given every two weeks and inclisiran given every 6 months are available. A randomized clinical end-point study with a large number of patients has not yet been completed with the latter, but studies have been conducted with this drug so far, and since this mechanism of action with PCSK9 inhibitor monoclonal antibodies has already been proven in clinical studies and Mendelian randomization studies, there is expert consensus that anticipating trust, inclisiran can be given safely and effectively. Pooled post hoc analyzes demonstrated an LDL-C-lowering effect of 45-55%, and analysis of 9,982 patient-years of 3,576 patients compared with placebo showed no difference in reported treatment-emergent adverse events and discontinuation of therapy.