Platelet function and activation markers in primary hypercholesterolemia treated with anti-PCSK9 monoclonal antibody: A 12-month follow-up

Background and aimsIn the association between hypercholesterolemia (HC) and thrombotic risk platelet hyper-reactivity plays an important role. The inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) to reduce plasma LDL-cholesterol merges as effective therapeutic strategy to prevent cardiovascular (CV) events. Aim of this study was to verify whether a treatment up to 12 months with the monoclonal antibodies (mAbs) anti-PCSK9 influences platelet function in primary HC.Methods and resultsIn patients affected by primary HC (n = 24), all on background of statin and 17 on acetyl salicylic acid (ASA), platelet function parameters were evaluated at baseline up to 12 months of treatment with the mAb anti-PCSK9 alirocumab or evolocumab.From baseline, the treatment with anti-PCSK9 mAbs: i) in ASA HC patients, significantly decreased platelet aggregation detected in platelet-rich plasma by light transmission aggregometry and in whole blood Platelet Function Analyzer-100 assay; ii) in all HC patients, significantly decreased platelet membrane expression of CD62P and plasma levels of the in vivo platelet activation markers soluble CD40 Ligand, Platelet Factor-4, and soluble P-Selectin. Furthermore, CD62P expression, and sP-Selectin, PF-4, sCD40L levels significantly correlated with serum PCSK9.ConclusionBesides markedly lowering LDL-c levels, our results suggest that HC patients benefit from anti-PCSK9 mAb treatment also for reducing platelet reactivity and increasing platelet sensitivity to the inhibitory effects of aspirin. These effects on platelets could play a role in the reduction of CV event incidence in patients treated with PCSK9 inhibitors.     

PCSK9 inhibitors in the prevention of cardiovascular disease

Reducing plasma levels of low-density lipoprotein cholesterol (LDL-C) remains the cornerstone in the primary and secondary prevention of cardiovascular disease. However, lack of efficacy and adverse effects mean that a substantial proportion of patients fail to achieve acceptable LDL-C levels with currently available lipid-lowering drugs. Over the last decade, inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic strategy to reduce residual cardiovascular disease risk. Binding of PCSK9 to the LDL receptor targets the receptor for lysosomal degradation. The recognition that inhibition of PCSK9 increases LDL receptor activity has led to the development of a number of approaches to directly target PCSK9. Numerous monoclonal antibodies against PCSK9 are currently being evaluated in phase 3 trials, involving various patient categories on different background lipid-lowering therapies. Current evidence shows reductions in LDL-C levels of up to 70 % may be achieved with PCSK9 inhibition, independent of background statin therapy. This review examines the most recent evidence and future prospects for the use of PCSK9 inhibitors in the prevention of cardiovascular disease.     

Association between plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) and lipids with rs7903146 polymorphisms of the TCF7L2 gene in diabetic patients

The rs7903146 polymorphism of TCF7L2 gene is known as the strongest genetic risk factor for type 2 diabetes mellitus (T2DM). The polymorphism is in association with clinical profile of T2DM patients. PCSK9 is a serine protease that promotes LDLR degradation and regulates circulating levels of lipids. The association of this polymorphism with PCSK9 and metabolic profile of diabetic and healthy subjects was investigated. This cross-sectional study was performed on 132 T2DM patients and the same number of healthy subjects. All the participants were genotyped for the rs7903146 single nucleotide polymorphism by the PCR-RFLP method. Metabolic profile including plasma levels of PCSK9, triglycerides, total cholesterol, non-HDL cholesterol, LDL cholesterol, HDL cholesterol, fasting plasma glucose, and HBA1C was measured. PCSK9, total cholesterol, and LDL-C levels were lower in the diabetic patients as compared to the healthy subjects. There were also direct and significant associations between PCSK9 and TG, TC, LDL-C, and non HDL-C in the subjects. Values of plasma glucose, HbA1c, PCSK9, TC, and LDL-C were higher in patients with TT genotype, but the differences were not statistically significant for all. A positive Spearman correlation was found between PCSK9 levels and the genotypes in all the participants. The results confirm the association of rs7903146 in the TCF7L2 gene with metabolic parameters and PCSK9. The T allele was associated with higher lipid and PCSK9 levels.

     

Differential Effects of DPP-4 Inhibitors,Anagliptin and Sitagliptin,on PCSK9 Levels in Patients with Type 2 Diabetes Mellitus who are Receiving Statin Therapy

Aim: Proprotein convertase subtilisin/kexin type 9 (PCSK9) degrades the low-density lipoprotein (LDL) receptor, leading to hypercholesterolemia and cardiovascular risk. Treatment with a statin leads to a compensatory increase in circulating PCSK9 level. Anagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was shown to decrease LDL cholesterol (LDL-C) levels to a greater extent than that by sitagliptin, another DPP-4 inhibitor, in the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. We investigated PCSK9 concentration in type 2 diabetes mellitus (T2DM) and the impact of treatment with anagliptin or sitagliptin on PCSK9 level as a sub-analysis of the REASON trial. Methods: PCSK9 concentration was measured at baseline and after 52 weeks of treatment with anagliptin ( n =122) or sitagliptin ( n =128) in patients with T2DM who were receiving statin therapy. All of the included patients had been treated with a DPP-4 inhibitor prior to randomization. Results: Baseline PCSK9 level was positively, but not significantly, correlated with LDL-C and was independently associated with platelet count and level of triglycerides. Concomitant with reduction of LDL-C, but not hemoglobin A1c (HbA1c), by anagliptin, PCSK9 level was significantly increased by treatment with sitagliptin (218±98 vs. 242±115 ng/mL, P =0.01), but not anagliptin (233±97 vs. 250±106 ng/mL, P =0.07). Conclusions: PCSK9 level is independently associated with platelet count and level of triglycerides, but not LDL-C, in patients with T2DM. Anagliptin reduces LDL-C level independent of HbA1c control in patients with T2DM who are on statin therapy possibly by suppressing excess statin-mediated PCSK9 induction and subsequent degradation of the LDL receptor.     

PCSK9-Inhibitoren

The 2 or 4?week subcutaneous therapy with the recently approved antibodies alirocumab and evolocumab for inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) reduces low-density lipoprotein cholesterol (LDL-C) in addition to statins and ezetimibe by 50–60?%. The therapy is well-tolerated. The safety profile in the published studies is comparable to placebo. Outcome data and information on long-term safety and the influence on cardiovascular events are not yet available but the results of several large trials are expected in 2016–2018. At present (spring 2016) PCSK9 inhibitors represent an option for selected patients with a high cardiovascular risk and high LDL-C despite treatment with the maximum tolerated oral lipid-lowering therapy. This group includes selected patients with familial hypercholesterolemia and high-risk individuals with statin-associated muscle symptoms (SAMS).     

From the Cover: A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum LDL cholesterol (LDL-C) by interacting with the LDL receptor (LDLR) and is an attractive therapeutic target for LDL-C lowering. We have generated a neutralizing anti-PCSK9 antibody, mAb1, that binds to an epitope on PCSK9 adjacent to the region required for LDLR interaction. In vitro, mAb1 inhibits PCSK9 binding to the LDLR and attenuates PCSK9-mediated reduction in LDLR protein levels, thereby increasing LDL uptake. A combination of mAb1 with a statin increases LDLR levels in HepG2 cells more than either treatment alone. In wild-type mice, mAb1 increases hepatic LDLR protein levels ≈2-fold and lowers total serum cholesterol by up to 36%: this effect is not observed in LDLR^−/− mice. In cynomolgus monkeys, a single injection of mAb1 reduces serum LDL-C by 80%, and a significant decrease is maintained for 10 days. We conclude that anti-PCSK9 antibodies may be effective therapeutics for treating hypercholesterolemia.     

Association between causative mutations and response to PCSK9 inhibitor therapy in subjects with familial hypercholesterolemia: A single center real-world study

Background and aimsFamilial hypercholesterolemia (FH) is an autosomal dominant disease that leads to cardiovascular (CV) disease. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-I) demonstrated efficacy in low-density lipoprotein cholesterol (LDL-C) reduction and in prevention of CV events. The aim of our study is to evaluate the relationship between LDL receptor (LDLR) mutations and response to PCSK9-I therapy.Methods and resultsWe evaluated total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) in consecutive patients with FH before PCSK9-I treatment and after 12 (T12w) and 36 (T36w) weeks of treatment. We evaluated LDL-C target achievement according to different mutations in LDLR. Eighty FH subjects (mean age:54 ± 13.3 years), 39 heterozygous (He) with defective LDLR gene mutations, 30 He with null mutations and 11 compound-He or homozygous (Ho) were recruited. At baseline, 69 subjects were under maximal lipid lowering therapy (MLLT) and 11 subjects had statin-intolerance. From baseline to T36w we observed an overall 51% reduction in LDL-C. We found no difference in LDL-C changes between subjects with He-defective mutation and He-null mutations both at T12w (p = 1.00) and T36w (p = 0.538). At T36w, LDL-C target was achieved in 59% of He-defective mutations subjects and in 36% of He-null mutations subgroup (p = 0.069), whereas none of compound-He/Ho-FH achieved LDL-C target.ConclusionsAfter 36 weeks there were no differences in response to PCSK9-I therapy between different groups of He-FH subjects. Response to PCSK9-I was significantly lower in carriers of compound-He/Ho mutations.Registration number for clinical trials: NCT04313270 extension.     

Positive correlation between plasma PCSK9 and tissue factors levels in patients with angiographically diagnosed coronary artery disease and diabetes mellitus

Background Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that influences plasma levels of low-density lipoprotein cholesterol (LDL-C). Both oxidized LDL and tissue factor (TF) contributed to the development of prothrombotic state. The present study aims to explore the relationship between plasma level of PCSK9 and that of TF in patient with coronary artery disease (CAD). Methods From July 2013 to March 2014, we enrolled 197 consecutive patients who underwent coronary angiography because of suspected CAD at Beijing Anzhen Hospital in this study. All patients had no history of using lipid-lowering medication. Of these 197 patients (131 male and 66 female, mean age 56.9 ± 11.8 years), 81 had angiographically diagnosed CAD. Clinical data were collected. Plasma PCSK9 and TF were measured using enzyme-linked immunosorbent assay (ELISA). Levels of plasma PCSK9 and TF were compared and their correlation analyzed among different patient groups. Results Both plasma levels of PCSK9 (279.8 ± 60.4 μg/L vs. 216.5 ± 45.3 μg/L, P < 0.01) and TF (156.4 ± 26.6 μg/mL vs. 112.1 ± 38.3 μg/L, P < 0.01) were significantly higher in patients with CAD, as compared with those with?out CAD. Correlation analysis showed plasma level of PCSK9 was significantly correlated with that of TF in both patients with and without CAD. However, multivariate regression analysis after adjustment for age, gender, smoking, alcohol, hypertension and hyperlipidemia showed that only in CAD patients with type 2 diabetes mellitus, there was significant positive correlation between plasma levels of PCSK9 and TF (β = 0.353, P < 0.01). Conclusions The plasma level of PCSK9 is independently and positively associated with that of TF in CAD patients with diabetes mellitus, but not in those without diabetes mellitus. Further study is needed to investigate the underlying mechanism.     

PCSK9 inhibitors in clinical practice: Novel directions and new experiences

BackgroundIn randomized clinical trials, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) effectively reduce low-density lipoprotein-cholesterol (LDL-C) with a favorable tolerability and safety profile. Our purpose is to provide real-world data regarding the indications, efficacy and safety of PCSK9i.MethodsThe cohort comprised 141 patients who attended the lipid clinic of 3 hospitals in Greece and started using PCSK9i. Patients were requested to attend the lipid clinic at 3 months and at 1 year.ResultsNinety percent of patients had heterozygous familial hypercholesterolaemia (heFH) and 75% had cardiovascular disease (CVD). A PCSK9i [evolocumab 140 mg/2 weeks (n = 82), alirocumab 75 mg/2 weeks (n = 46) and alirocumab 150 mg/2 weeks (n = 13)] was prescribed due to failure to achieve LDL-C targets despite maximum lipid-lowering therapy (LLT) in 75% of patients, while in the remaining cases, the indication was statin intolerance. The mean reduction of LDL-C at 3 months was 56.2% and remained constant at 12 months (55.8% reduction from baseline). LDL-C target was achieved by 68.1% of patients at 3 months. “Totally” intolerant to statins patients (unable to tolerate any statin dose, n = 23) showed the lowest LDL-C reduction (47.7%). Side effects attributed to treatment were reported by 14 patients (10%). The total number of patients who stopped PCSK9i at 1 year was 14 (10%) but only 2 (1.4%) discontinued treatment because of side effects (myalgias).ConclusionsOur real-world results of PCSK9i showed comparable efficacy and tolerability to those reported in clinical trials and highlighted the value of treatment with PCSK9i heFH patients not achieving LDL-C targets despite maximum LLT and high or very high risk statin intolerant patients.     

前蛋白转化酶枯草溶菌素9抑制剂与血小板功能

前蛋白转化酶枯草溶菌素9 (PCSK9)抑制剂能显著地降低血浆低密度脂蛋白胆固醇水平,是高脂血症治疗和高危心血管疾病患者二级预防有潜力的手段.越来越多的证据表明,PCSK9抑制剂降低心血管事件的作用可能部分归因于其对血小板功能的影响.PCSK9抑制剂既可通过抑制PCSK9直接降低血小板功能,也可通过调节脂质水平间接降低...     

New and Emerging Therapies for Reduction of LDL-Cholesterol and Apolipoprotein B: JACC Focus Seminar 1/4

Adding to the foundation of statins, ezetimibe and proprotein convertase subtilisin–kexin type 9 inhibitors (PCSK9i), novel, emerging low-density lipoprotein cholesterol (LDL-C)–lowering therapies are under development for the prevention of cardiovascular disease. Inclisiran, a small interfering RNA molecule that inhibits PCSK9, only needs to be dosed twice a year and has the potential to help overcome current barriers to persistence and adherence to lipid-lowering therapies. Bempedoic acid, which lowers LDL-C upstream from statins, provides a novel alternative for patients with statin intolerance. Angiopoetin-like 3 protein (ANGPTL3) inhibitors have been shown to provide potent LDL-C lowering in patients with homozygous familial hypercholesterolemia without major adverse effects as seen with lomitapide and mipomersen, and may reduce the need for apheresis. Finally, CETP inhibitors may yet be effective with the development of obicetrapib. These novel agents provide the clinician the tools to effectively lower LDL-C across the entire range of LDL-C–induced elevation of cardiovascular risk, from primary prevention and secondary prevention to null-null homozygous familial hypercholesterolemia patients.     

Effectiveness of proprotein convertase subtilisin/kexin‐9 monoclonal antibody treatment on plasma lipoprotein(a) concentrations in patients with elevated lipoprotein(a) attending a clinic

BackgroundLipoprotein(a) (Lp[a]) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Proprotein convertase subtilisin/kexin‐9 monoclonal antibodies (PCSK9mAbs) can lower Lp(a) levels in clinical trials, but their effects in patients with elevated Lp(a) in clinical practice remain unclear.AimsTo investigate the effectiveness and safety of PCSK9mAbs in lowering plasma Lp(a) in patients with elevated Lp(a) concentrations in a lipid clinic.MethodsThis was an open‐label study of 53 adult patients with elevated Lp(a) concentration (≥0.5 g/L). Clinical, biochemical, and safety data were collected before and on treatment with evolocumab or alirocumab over a mean period of 11 months.ResultsTreatment with a PCSK9mAb resulted in a significant reduction of 0.29 g/L (−22%) in plasma Lp(a) concentration (p<.001). There were also significant reductions in low‐density lipoprotein‐cholesterol (LDL‐C) (−53%), remnant‐cholesterol (−12%) and apolipoprotein B (−43%) concentrations. The change in Lp(a) concentration was significantly different from a comparable group of 35 patients with elevated Lp(a) who were not treated with a PCSK9mAb (−22% vs. −2%, p<.001). The reduction in Lp(a) concentration was not associated with the corresponding changes in LDL‐C, remnant‐cholesterol, and apolipoprotein B (p>.05 in all). 7.5% and 47% of the patients attained a target concentration of Lp(a) <0.5 g/L and LDL‐C <1.8 mmol/L, respectively. PCSK9mAbs were well tolerated, the common adverse effects being pharyngitis (9.4%), nasal congestion (7.6%), myalgia (9.4%), diarrhoea (7.6%), arthralgia (9.4%) and injection site reactions (11%).ConclusionPCSK9mAbs can effectively and safely lower plasma Lp(a) concentrations in patients with elevated Lp(a) in clinical practice; the impact of the fall in Lp(a) on ASCVD outcomes requires further investigation.     

PCSK9抑制剂的临床研究进展

前白蛋白转化酶枯草菌素9(proprotein convertase subtilisin/Kexin type 9,PCSK9)是一种参与脂质调节的丝氨酸蛋白酶.PCSK9抑制剂是通过不同途径抑制PCSK9功能的物质.从2003年发现PCSK9基因突变到2015年两种PCSK9单克隆抗体上市的这个过程,是一个典型的从...     

Efficacy and safety of PCSK9 inhibitors in patients with diabetes: A systematic review and meta-analysis

AimsIndividuals with diabetes have increased cardiovascular risk. Although PCSK9 inhibitors bring about a wide reduction in lipids, there is uncertainty about the effects for diabetic patients. We conducted a systematic review and meta-analysis to assess the efficacy and safety of PCSK9 inhibitors for diabetes.Data synthesisWe performed a meta-analysis comparing treatment with PCSK9 inhibitors versus controls up to July 2022. Primary efficacy endpoints were percentage changes in lipid profile parameters. We used random effects meta-analyses to combine data. Subgroups of diabetic patients (by diabetes type, baseline LDL-C, baseline HbA1c and follow-up time) were also compared. We included 12 RCTs comprising 14,702 patients. Mean reductions in LDL-C were 48.20% (95% CI: 35.23%, 61.17%) in patients with diabetes. Reductions observed with PCSK9 inhibitors were 45.23% (95% CI: 39.43%, 51.02%) for non-HDL-cholesterol, 30.39% (95% CI: 24.61%, 36.17%) for total cholesterol, 11.96% (95% CI: 6.73%, 17.19%) for triglycerides, 27.87% (95% CI: 22.500%, 33.17%) for lipoprotein(a), 42.43% (95% CI: 36.81%, 48.06%) for apolipoprotein B; increases in HDL-C of 5.97% (95% CI: 4.59%, 7.35%) were also observed. There was no significant difference in fasting plasma glucose (FPG) (WMD: 2.02 mg/mL; 95% CI: −1.83, 5.87) and HbA1c (WMD: 1.82%; 95% CI: −0.63, 4.27). Use of a PCSK9 inhibitor was not associated with increased risk of treatment-emergent adverse event (TEAE) (p = 0.542), serious adverse event (SAE) (p = 0.529) and discontinuations due to AEs (p = 0.897).ConclusionsPCSK9 inhibitor therapy should be considered for all diabetic individuals at high risk of atherosclerotic cardiovascular disease.Registration code in prosperoCRD42022339785.     

PCSK9抑制剂治疗超高危ASCVD的降脂有效性与安全性

目的 观察PCSK9抑制剂对超高危动脉粥样硬化性心血管疾病（atherosclerotic cardiovascular disease,ASCVD）患者的降脂治疗有效性与安全性。 方法 收集2017年9月～2020年3月于空军军医大学第一附属医院接受PCI治疗的超高危ASCVD患者138例,划分为术后单纯他汀类药物降脂治疗的他汀对照组（n=100）和他汀联合PCSK9降脂治疗的PCSK9抑制剂组（n=38）。用药3月后复查血脂水平,观察血脂降幅及药物不良反应发生情况。 结果 两组患者年龄、BMI、收缩压、舒张压等多项指标差异无统计学意义。与他汀对照组比较,PCSK9抑制剂组的男性比例低,既往心肌梗死病史率低,多次PCI史率低（P<0.01）,多血管床病变率低,术后应用β-受体阻滞剂率低（P<0.05）。接受降脂治疗后与他汀对照组比较,PCSK9抑制剂组LDL-C明显降低,其中低密度脂蛋白胆固醇（LDL-C）（<1.4 mmol/L）组和LDL-C平均降幅降低程度的统计学差异为（P<0.01）,LDL-C(<1.8 mmol/L)组降低的统计学差异为（P<0.05）。所有患者均未观察到肝肾功损害及血糖升高,PCSK9抑制剂组患者未观察到药物不良反应的发生。 结论 PCSK9抑制剂能够有效降低超高危ASCVD患者的LDL-C水平,显著提高其LDL-C达标率,具有良好的有效性和安全性。     

后他汀时代的调脂治疗策略

他汀类药物降低LDL-C可以显著减少心血管事件,但2型糖尿病患者经过他汀类药物治疗后仍面临很高的心血管剩留风险。高TG和低HDL-C是2型糖尿病主要异常血脂表型。高TG导致LDL颗粒改变,形成的小而密LDL颗粒(LDL-P),易于致动脉粥样硬化。LDL-P较LDL-C预测未来心血管事件更加敏感,LDL-P和载脂蛋白B(ApoB)较LDL-C与代谢综合征的危险程度相关性更显著。非诺贝特可以显著降低代谢综合征患者LDL-P浓度。对于糖尿病和代谢综合征人群,在应用他汀类药物治疗后,尚存在高TG、低HDL-C和高ApoB(LDL-P)异常血脂谱的患者,联用非诺贝特类药物降低血管剩留风险,应当是他汀类药物治疗后的调脂治疗策略。     

Fenofibrate concomitantly decreases serum proprotein convertase subtilisin/kexin type 9 and very‐low‐density lipoprotein particle concentrations in statin‐treated type 2 diabetic patients

Aim: Diabetic dyslipidaemia, characterized by hypertriglyceridaemia as a result of elevated serum very‐low‐density lipoprotein (VLDL) concentrations, contributes to the increased risk of cardiovascular disease (CVD) in type 2 diabetes (T2DM). Proprotein convertase subtilisin/kexin type 9 (PCSK9) may play a role in regulating VLDL metabolism. We investigated the effect of fenofibrate on serum PCSK9 and VLDL particle concentrations in T2DM patients already receiving statin therapy. Methods: In a double‐blind randomized crossover study, 15 statin‐treated T2DM patients (63 ± 8 years, body mass index (BMI) 29 ± 3 kg/m²) were treated with fenofibrate (145 mg/day) or matching placebo for 12 weeks. Serum PCSK9 concentrations were measured by immunoassay. VLDL particle concentration and size were determined by nuclear magnetic resonance spectroscopy. Results: Fenofibrate decreased serum triglycerides (?23%), VLDL‐triglycerides (?51%), total cholesterol (?11%), LDL‐cholesterol (?16%), apolipoprotein B‐100 (?16%), apolipoprotein C‐III (?20%) and PCSK9 (?13%) concentrations compared with placebo (p < 0.05). Fenofibrate also decreased serum concentrations of large (?45%), medium (?66%) and small VLDL (?67%) particles (p < 0.05), without altering VLDL particle size. Serum PCSK9 reduction correlated with decreases in total (r = 0.526, p = 0.044) and small (r = 0.629, p = 0.021) VLDL particle concentrations. Conclusions: Fenofibrate concomitantly decreased serum PCSK9 and VLDL particle concentrations in statin‐treated T2DM patients. These findings support a mechanistic link between PCSK9 and VLDL metabolism, possibly through an effect of PSK9 on VLDL receptor degradation.     

前蛋白转化酶枯草溶菌素9抑制剂的临床研究及应用进展

前蛋白转化酶枯草溶菌素9(PCSK9)抑制剂可通过抑制肝细胞表面低密度脂蛋白受体的降解对脂质代谢起到调节作用。目前已有多项临床研究证明,PCSK9抑制剂单一药物或与他汀类药物联合使用可显著降低低密度脂蛋白胆固醇水平。本文综述了当前PCSK9抑制剂的重要临床研究及应用进展,并简要总结了常见PCSK9抑制剂的安全性、有效性及临床应用现状。     

PCSK9抑制剂在动脉粥样硬化性心血管疾病中的抗炎作用研究进展

高脂血症是动脉粥样硬化性心血管疾病（ASCVD）的重要危险因素,降脂治疗是ASCVD治疗的重要内容。近些年来,前蛋白转化酶枯草溶菌素 9（proprotein convertase subtilisin/kexintype9,PCSK9）抑制剂被证实具有强效的降低低密度脂蛋白胆固醇（low density lipoprotein cholesterol,LDL-C）的作用,并被多个降脂指南推荐作为降脂治疗的重要方法。随着研究的深入,PCSK9抑制剂除具有降低LDL-C作用外,还发挥一定程度的抗炎作用。本文从PCSK9参与炎症反应角度出发,对PCSK9抑制剂在ASCVD中的抗炎作用作一综述。