The Observation Of The Early Efficacy Of PCSK9 Inhibitors-Evolocumab In Ultra-high-risk ACS Patients

Background and ObjectivePatients with acute coronary syndrome(ACS)have a high risk of recurrent ischemic events,especially in the early stages of the disease.Lowering low-density lipoprotein cholesterol(LDL-C)can reduce the incidence of cardiovascular events in patients.Although stains,as the cornerstone of lipid-lowing therapy,can reduce the incidence of cardiovascular events in the early stage of ACS,often have a slow onset of action,and stain therapy alone often fails to achieve therapeutic goals in patients with ultra-high-risk ACS.Therefore,rapidly and effectively lowering LDL-C has become one of the key issues in the treatment of ACS.Human proprotein convertase subtilisin Kexin type 9(PCSK9)inhibitor,as a fully human monoclonal antibody,has a fast onset of action large lipid-lowering rate,and large compliance rate.A lot of evidence has shown its advantages in lowering LDL-C levels and significantly reducing cardiovascular events.However,there are few reports on the early treatment effect of PCSK9 inhibitors in ultra-high-risk ACS patients.In addition,the level of PCSK9 increases in the acute phase of ACS,which can participate in the inflammatory response in the body in various ways,leading to the increase of inflammatory indicators in the body.High sensitivity C-reactive protein(hsCRP),as the most widely used test index to quantify inflammation in cardiovascular diseases(CVD),has different effects on hsCRP after the application of PCSK9 inhibitors.Therefore,our study protocol observed the changes in early blood lipid indexes and inflammatory indexes in ultra-high-risk ACS patients with PCSK9 inhibitor-Evolocumab,to provide evidence for early prevention and treatment of ACS patients.MethodsUsing the method of observational study,94 patients with ultra-high-risk ACS who were admitted to the Department of Cardiology,The First Affiliated Hospital of Zhengzhou University from December 2019 to December 2021 were consecutively enrolled according to the inclusion and exclusion criteria.These patients were subcutaneously injected with Evolocumab(trade name:Rui Baian,manufacturer:Amgen Manufacturing Limited,approval number:Imported Drug Registration No.S20180021).According to the drug instructions and the patient’s medication situation,they were divided into a group of 1 dose(140 mg)twice a month(50 cases in total,hereinafter referred to as the 2-arm group)and a group of 3 doses(420 mg)once a month(44 cases in total,hereinafter referred to as the 3-arm group).Observe changes in LDL-C,total cholesterol(TC),triglycerides(TG),high-density lipoprotein(HDLC),lipoprotein a[Lp(a)],hsCRP at 12-24 hours,3 days,7 days,15 days,and 30 days after treatment.The major adverse cardiovascular and cerebrovascular events(MACCE),such as cardiovascular death,myocardial infarction(MI),stroke,hospitalization for unstable angina,coronary revascularization,and other major adverse cardiovascular and cerebrovascular events,occur during the observation period.And whether there are adverse reactions,such as injection site reactions,allergic reactions,muscle-related events,abnormal liver function,abnormal renal function,elevated myocardial enzymes,cognitive dysfunction,etc.SPSS 21.0 statistical software was used for data analysis,and P<0.05 was considered to be statistically significant.Results1.The effect of PCSK9 inhibitor on LDL-C level:12-24 hours after the application of PCSK9 inhibitor-Evolocumab,the level of LDL-C in both groups decreased greater than or equal to 30%within 12-24 hours,and there was no statistical difference between the two groups(P=0.886);the 2-arm group reached the lowest value at 15 days after treatment,with a decrease of(65.60±19.24)%,and the 3-arm group was the lowest at 7 days after treatment,with a decrease of(75.29±15.18)%.At different time points,there were significant differences between the two groups in the 3 days and 7 days after treatment(P<0.05).2.PCSK9 inhibitors also have a certain reducing effect on TC,and the changing trend is similar to that of LDL-C.3.The effect of PCSK9 inhibition on TG:PCSK9 inhibitors can also rapidly reduce the level of TG,2-arm groups reached the lowest at 15 days after treatment,and 3-arm groups reached the lowest at 30 days after treatment.4.The effect of PCSK9 inhibitors on HDL-C:PCSK9 inhibitors have an increasing effect on HDL-C,and the increase is the highest 30 days after administration.The increase rates of the 2-arm group and the 3-arm group were 11.15%and 10.20%.There was no significant difference in the increase rates between the two groups(P=0.703).5.The effect of PCSK9 inhibitors on Lp(a):Both groups’Lp(a)levels decreased rapidly 12-24 hours after treatment,and the decrease in the 2-arm group reached the maximum at 15 days after treatment,which was 36.59%;The 7-day decrease was the largest in a three-arm group,which was 41.64%;the decrease between the two groups was significantly different at 3 days,7 days,and 30 days after treatment(P<0.05).6.The changes of hsCRP after medication:hsCRP showed a trend of first increase and then decrease after medication,and there was no significant difference between the two groups.Further grouped by the level of hsCRP,divided into the high-level group,middle-level group,and low-level group.In the high-level group,hsCRP decreased significantly after medication,and the middle and low-level groups showed a trend of increasing firstly and then decreasing after medication.7.During the observation period,there was occurred MACCE and serious adverse events.There was no statistically significant difference in adverse events between the two groups.Conclusions1.PCSK9 inhibitors can rapidly reduce the level of LDL-C in patients with ultrahigh-risk ACS in the early stage,and the decrease of 420 mg in a single month is more obvious,thus playing a role in the prevention and treatment of early cardiovascular events in patients with ultra-high-risk ACSit also has a certain reduction effect on TG and TC,simultaneously increased HDL-C levels.2.PCSK9 inhibitors can also rapidly reduce the level of Lp(a),further reducing cardiovascular events in ultra-high-risk ACS patients.3.After the application of the PCSK9 inhibitor,it has a certain inhibitory effect on the inflammatory response in vivo,especially in the high hsCRP level,which may be one of the mechanisms by which PCSK9 inhibitor reduces cardiovascular events in ACS.