Effects Of PCSK9 Inhibitors On ACS Patients With Type 2 Diabetes Mellitus After PCI

Background and ObjectivesCardiovascular disease,the morbidity and mortality of which are rising year by year globally including China,is the leading cause of death worldwide,bringing tremendous pressures and public health problems to all countries.Diabetes,as one of the most important risk factors for cardiovascular disease,not only increases the risk of suffering from coronary heart disease(CHD),but also predicts poor survival outcomes of CHD patients.A great number of people in China are exposed to this risk factor,considering that the prevalence of diabetes has surged in the last decades of years.CHD patients with diabetes account for a large proportion of all patients that receive percutaneous coronary intervention(PCI).Hyperglycemia and diabetic dyslipidemia in type 2 diabetes mellitus are thought to be closely associated with cardiovascular disease,and the guidelines emphasize achieving targeted lipids levels by lipid-lowering therapy(LLT)to lower the risk of cardiovascular disease,especially in patients with acute coronary syndrome(ACS)and diabetes.Low-density lipoprotein cholesterol(LDL-C)is recommended for the primary target of lipid-lowering therapy.Currently,statin-based lipid-lowering regimen is the cornerstone of lipid management,but only a minority of patients succeeded in reaching the optimal LDL-C targets,though they underwent maximum tolerated LLT.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors have been adopted by guidelines for lipid control owing to their robust lipid-lowering effects.Several randomized controlled clinical trials have shown that PCSK9 inhibitors(PCSK9i)can reduce LDL-C significantly,while decreasing the incidence of cardiovascular events,including major adverse cardiovascular events(MACE).But there is no sufficient data available to unveil the therapeutic effects of PCSK9 i on ACS patients with type 2 diabetes mellitus after PCI in real-world conditions.In addition,PCSK9 i have been found to show a certain level of anti-inflammatory effect recently,but commonly used inflammatory indices are not influenced by them.Hematological indices and derived inflammatory markers play roles in risk stratification,prognosis judgment and guiding treatment of cardiovascular diseases,while whether PCSK9 i effect on these inflammatory indexes is unclear.This is a real-world study to investigate the effects of PCSK9 inhibitors on ACS patients with type 2 diabetes mellitus after PCI,including the lipid-lowering effects,the impact on cardiovascular events,and the adverse effects on liver and renal functions.Additionally,we tried to explore the differences of hematological indices and derived inflammatory markers in post-hoc analysis.MethodsPatients who admitted by the Department of Cardiology of Xijing Hospital for ACS with type 2 diabetes from October 2021 to December 2021 and successfully underwent PCI were included.Patients were classified into PCSK9 i group and only statin group.Baseline information of eligible individuals were collected,including general demographic conditions,previous medical history,history of present illness,medical treatment,relevant laboratory tests,and occurrence of cardiovascular events.The primary endpoint of this study was the lipid-lowering effects of PCSK9 inhibitors,which focused on the change of LDL-C from baseline to 16 weeks.Secondary endpoints were adverse cardiovascular events including MACE at 48 weeks,changes in concentrations of high-density lipoprotein cholesterol(HDL),non-high-density lipoprotein cholesterol(non-HDL-C),total cholesterol(TC)and triglycerides(TG)at 16 weeks,and effects on liver and renal functions.Post-hoc exploratory analyses of changes in hematological indices and derived inflammatory markers at 16 weeks were also conducted.ResultsA total of 482 patients were included,and 402 patients were selected after screening,including 83 cases in the PCSK9 i group and 319 cases in the statin group.At weeks 16,the LDL-C concentrations of the PCSK9 i group and statin control group were 0.72 ± 0.22 and 1.55±0.34mmol/L(P<0.001),respectively.The absolute changes were 1.43±0.79 and0.79±0.71mmol/L(P<0.001),and percent changes from baseline were 62.5±17.1 and28.1±20.0%(P<0.001)respectively.After treatment,the LDL-C concentrations of Evolocumab and Alirocumab groups were 0.72± 0.19,0.73± 0.24 mmol/L,and there was no significant difference between them(P=0.75).In terms of non-HDL-C,TC and TG,PCSK9 i reduced extra 0.85(P<0.001),0.84(P<0.001)and 0.32mmol/L(P<0.001)compared with statin.There were no significant differences in HDL-C concentrations,cardiovascular adverse event rates,or liver and renal functional indexes between the two groups.Covariance analysis showed that there were statistically differences in the changes of platelet and lymphocyte-to-monocyte ratio(LMR)between groups before propensity score matching(PSM).After PSM,there were statistical differences in lymphocyte,platelet distribution width(PDW),mean platelet volume(MPV)and LMR.Conclusion1.PCSK9 inhibitors exert immense lipid-lowering potential,and there are no obvious differences in lipid-lowering efficacy between Alirocumab and Evolocumab at 16 weeks.Baseline LDL-C levels can affect the lipid-lowering efficacy of statins but not PCSK9 inhibitors within 16 weeks,which provides a realistic basis for clinicians to choose appropriate regimens according to lipid-lowering goals,lipid levels,and patients’ choices.2.PCSK9 inhibitors show no extra impact on liver and renal functions at 16 weeks,and no influence on incidences of adverse cardiovascular events at 48 weeks compared with statins.3.PCSK9 inhibitors can lower a part of hematological indices and derived inflammatory markers more than statins at 16 weeks,but the results need to be further evaluated by more rigorous studies.