The following items were extracted from included studies: first authors name, year of publication, study design, characteristic of patients, sample size, duration of intervention and type of control, drug dose, clinical outcomes, and adverse events

The following items were extracted from included studies: first authors name, year of publication, study design, characteristic of patients, sample size, duration of intervention and type of control, drug dose, clinical outcomes, and adverse events. ?50.13), triglycerides (MD=?12.21?mg/dL, 95% CI: ?16.21 to ?8.22) and apolipoprotein-B (MD=?41.01?mg/dL, 95% CI: ?46.07 to ?35.94), lipoprotein(a) (standardized mean difference=?0.94, 95% CI: ?1.12 to ?0.77) and increased the levels of high-density lipoprotein cholesterol (MD=3.40?mg/dL, 95% CI: 3.12 to 3.68) and apolipoprotein-A1 (MD=6.75?mg/dL, 95% CI: 4.64 to 8.86). There was no significant difference in the incidence of treatment-emergent adverse events (risk ratio=1.01, 95% CI: 0.98 to 1 1.04), serious treatment-emergent adverse events (risk ratio=1.01, 95% CI: 0.88 to 1 1.17), and the discontinuation of treatment between the 2 groups (risk ratio=1.07, 95% CI: 0.86 to 1 1.34). Conclusions The meta-analysis indicated that PCSK9 inhibitors had a strong effect in lowering low-density lipoprotein cholesterol and other lipid levels with satisfactory safety and tolerability in patients with hypercholesterolemia. Keywords: lipids, lipoproteins, meta-analysis, proprotein convertase subtilisin/kexin9 inhibitor Despite advances in the detection and treatment of ischemic cardiovascular disease (CVD), such as myocardial infarction and stroke in recent years, it remains the leading cause of death worldwide.1 Low-density lipoprotein cholesterol (LDL-C) is the primary atherogenic lipoprotein, and LDL-C reduction is the target of primary or secondary prevention of CVD.2 Statins are considered the most effective agents for reducing LDL-C and decrease the risk for CVD events.3,4 It is recommended to prescribe high-intensity statin therapy for individuals with high risk of CVD.5 However, broad spectrums of high-risk patients Rabbit Polyclonal to KSR2 fail to attain the guideline-recommended LDL-C goals due to statin intolerance and/or very high baseline levels (eg, familial hypercholesterolemia patients).6 Combination therapies that add nonstatin drugs are compromising methods in patients who are intolerant to high-intensity statin therapy.7 Recent studies revealed that adding ezetimibe to?simvastatin modestly reduced LDL-C (15?mg/dL) and CVD risks.8 However, other effective therapies are needed as alternative methods to further decrease LDL-C and finally reduce the mortality and morbidity of CVD. Proprotein convertase subtilisin/kexin9 (PCSK9) plays a pivotal role in regulating cholesterol homeostasis; it acts by binding to the LDL-receptor (LDL-R) at the surface of hepatocytes, hence promoting the clearance of LDL-R in lysosomes/endosomes, and results in decreased amount of LDL-R number and increased plasma HDL-C levels, so it has emerged as a stylish target for lowering LDL-C levels.9 The single-nucleotide polymorphism in PCSK9 gene are associated with LDL-C and risk of CVD, making PCSK9 inhibition a potential therapeutic modality.10C13 Statin therapy can increase plasma PCSK9 levels to some extent, while combination Didox with PCSK9 inhibitors may compensate this secondary change.14 Various Didox approaches have been tested to inhibit PCSK9 in active clinical and preclinical trials. Among those strategies, PCSK9 monoclonal antibody is usually of great interest because it blocks its binding to LDL-R via an allosteric mechanism.15 The human monoclonal antibodies against PCSK9 primarily include AMG145/Evolocumab, REGN727/SAR236553, and RN316/bococizumab.16 In the last 2?years, some early clinical trials have shown that PCSK9 inhibitors can reduce the plasma LDL-C level in patients with familial or nonfamilial hypercholesterolemia. The other lipids and lipoproteins such Didox as total cholesterol (TC), triglycerides (TG), high-density lipoprotein-C (HDL-C), apolipoprotein-B (Apo-B), Apo-A1, and lipoprotein(a) could also benefit from this approach. Because of differences in study design and Didox clinical outcomes, including dyslipidemia types, medicine dosage and therapeutic duration, and the Didox efficiency and safety of PCSK9 inhibitors that each author reported, greatly vary. To date, there is no report of any comprehensive and quantitative evaluation of the efficiency and safety of PCSK9 inhibitors therapy. The purpose of this.