hes the liver and consequently the expression of LDL receptors (LDLR) on the surface of hepatocytes is elevated, thus escalating liver uptake of endogenous cholesterol contained in LDL lipoproteins [160]. Ezetimibe monotherapy in a dose of 10 mg reduces LDL-C concentration by 155 ; even so, really a LTC4 medchemexpress higher inter-individual variability is observed [161]. This is determined by dietary variability (the lipid-lowering Bcl-B custom synthesis effect in the agent is elevated having a high-cholesterol diet) and probably the variability of genes encoding NPC1L1; for that reason, the response to ezetimibe alone could possibly be significantly far better within a specific group of sufferers [162]. This agent reduces TG concentration by 1.7.4 and increases HDL-C concentration to a little extent by 1.3.2 [163]. Nevertheless, information on the effect of ezetimibe on lipoprotein (a) are inconsistent, though all indicate a numerical Lp(a) reduction (from 2.6 to 7.1 ) [164, 165]. Nevertheless, following a meta-analysis by Tsimikas et al. [166] indicating a moderate but statistically significant (even though probably clinically insignificant) boost of Lp(a) concentration following statin treatment by six , specifically in high-risk patients with elevated concentration of this lipoprotein, combination therapy having a statin and ezetimibe is suggested [167]. Combination therapy with ezetimibe plus a statin, as a result of a synergistic effect, resultsin greater LDL-C concentration decrease than monotherapy with either agent [168]. Ezetimibe added to a statin reduces LDL-C concentration by one more 150 ; thus, a mixture of high-intensity statin therapy (i.e., atorvastatin or rosuvastatin at their highest doses) with ezetimibe can cut down LDL-C concentration by up to 650 [8, 9]. This mixture is much more powerful (by more than 15 mg/dl) in terms of LDL-C reduction and 2.45 occasions a lot more helpful in reaching the remedy target as when compared with doubling the statin dose [155, 168]. However, the combination of a statin with ezetimibe is still incredibly hardly ever made use of not just in Poland and in Europe, but also worldwide, although for four years ezetimibe has been a generic and quite affordable product. In the Da Vinci study, the mixture therapy was utilised only in 9.two of individuals [30], whereas in Central and Eastern European countries, in 7 [31]. This can be only a little increase from the 2016/2017 information in which, based on the TERCET registry, combination therapy having a statin and ezetimibe was utilised only in much less than three of ACS individuals [169] (Figure 4). In published randomised trials with ezetimibe, higher lipid-lowering efficacy and favorable security profile of combination therapy in sufferers with familial hypercholesterolaemia, renal failure, variety 2 diabetes mellitus, metabolic syndrome, higher cardiovascular threat, and ACS was demonstrated [8, 9, 170, 171]. In all these research, within the group receiving combination therapy, the target LDL-C concentration was accomplished significantly much more typically, and greater reduction of TC, non-HDL-C, TG and ApoB concentration was observed than with statin monotherapy [8, 9]. Furthermore, the results of IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) study demonstrated that LDL-C reduction with ezetimibe drastically reduces the incidence of cardiovascular events, as well as the greater the patient’s baseline cardiovascular danger, the larger the reduction [170, 171]. Ezetimibe is swiftly absorbed from the gastrointestinal tract, primarily as the pharmacologically active