Many patients with controlled LDLc have a persistently high concentration of atherogenic particles. convertase subtilisin/kexin type 9 (PCSK9) Phellodendrine chloride inhibitors are other drug classes which have been investigated for their potential to decrease LDLc. PCSK9 have been approved for the treatment of hypercholesterolemia and for the secondary prevention of cardiovascular events. The present narrative evaluate discusses the latest (2019) guidelines of the European Atherosclerosis Society/European Society of Cardiology for the management of dyslipidemia, focusing on LDLc-lowering drugs that are either already available on the market or under development. We also consider whom, when and how do we treat in Phellodendrine chloride Phellodendrine chloride terms of LDLc reduction in the daily clinical practice. Keywords: Dyslipidemia, LDL-cholesterol, Atherosclerosis, Statins, PCSK9 inhibitors Introduction The association between dyslipidemia and cardiovascular atherosclerotic disease is usually well established. In the last 50?years, a number of clinical and epidemiological studies have shown that increased levels of LDL cholesterol (LDLc) and low levels of HDL cholesterol (HDLc) correlate with the development and progression of atherosclerotic lesions. The discovery of -Hydroxy -methylglutaryl-CoA (HMG CoA) reductase inhibitors (statins) truly revolutionised the prevention and treatment of cardiovascular diseases. In the years that followed the introduction of statins in clinical practice, the management of dyslipidemia was mostly based on these drugs. Recently, several drug classes with cholesterol-lowering effects have been tested and approved for the treatment of dyslipidemic patients in whom standard therapy (statins, ezetimibe, and bile acid sequestrants) did not efficiently control lipid values. Such drugs include anti-pro-protein convertase subtilisin/kexin type 9, apolipoprotein(a) antisense oligonucleotide and microsomal triglyceride transfer protein inhibitors. As clinicians, the main questions we inquire ourselves when managing dyslipidemic patients are: Whom do we treat?, When is the initiation of a pharmacological agent justified? When do we consider the treatment to be effective and when do we need to switch our approach? and What is the optimal treatment and which drugs do we use? In this narrative review, we focused on whom, when and how do we treat in terms of LDLc reduction in the daily clinical practice. This approach will help physicians to efficiently reduce the cardiovascular risk of their patients via lipid profile improvement. Also, we present LDLc reduction strategies in some particular clinical settings, such as chronic kidney disease, autoimmune disorders and elderly patients, as well as a short description of the new emerging LDLc-lowering drugs that are in the pharmaceutical pipelines or in different stages of clinical trials. Whom do we treat? The decision to start lipid-lowering treatment in a specific patient is based on the analysis of lipid fractions (the ones associated with a high cardiovascular risk) and its correlation with the presence of other cardiovascular risk factors, as well as the analysis and estimation of the total cardiovascular risk. Strong evidence, derived from multiple studies, shows that the reduction of LDLc using statin treatment leads to a significant decrease in the cardiovascular risk, both in terms of primary prevention, as well as in the secondary prevention of cardiovascular events [1, 2]. Despite the fact that statins reduce the cardiovascular risk by 15 up to 37%, a substantial residual risk of 60C80% still remains [3]. This residual risk is due to an inadequate LDLc reduction, low levels of Phellodendrine chloride HDLc and high levels of triglycerides (TG) [4, 5]. The baseline lipid evaluation includes total cholesterol, HDLc, LDLc, TG, non-HDLc and the total cholesterol/HDLc ratio. The latest European guidelines for the management of dyslipidemia recommend that LDLc levels should be the main target of dyslipidemia treatment [6]. The secondary treatment targets are non-HDLc and apolipoprotein B (apoB), because these lipid fractions have not been extensively analyzed in randomized, controlled clinical trials. However, this hierarchy is usually disputed. Of particular interest to experts is usually apoB, which seems to predict cardiovascular risk as well as LDLc or more accurately [7]. One meta-analysis showed the superiority of apoB over non-HDLc and LDLc and concluded that among these three lipid fractions, LDLc was the weakest predictor of cardiovascular risk [8]. Moreover, LDLc cannot be accurately used to estimate the concentration of LDL particles when the patient also suffers from hypertriglyceridemia, a disadvantage that can be avoided by dosing apoB. The estimation of Phellodendrine chloride the total cardiovascular risk is based on the idea that the main atherogenic lipid component is usually cholesterol. This risk, however, seems to be correlated more with the FLJ22263 number of atherogenic particles (each one made up of an apolipoprotein B molecule) that penetrate the arterial wall, rather than the cholesterol concentration of these fractions.
