The Short-term Lipid-lowering Efficacy And Safety Analysis Of PCSK9 Inhibitor Evolocumab In Extremely High-risk Patients With Acute Coronary Syndrome

Objective:To explore the effects of combination group(Evolocumab + rosuvastatin calcium tablets)and the single group(rosuvastatin calcium tablets)on the changes of blood lipids;and to evaluate the efficacy and safety of both of them therapy for the extremely high-risk patients with acute coronary syndrome(acute coronary syndrome,ACS).Methods:From January 2020 to December 2020,total 86 for the extremely high-risk patients with ACS were randomly divided into combination group(n =41)and the single group(n=45).The conditions for the high-risk stratification of atherosclerotic cardiovascular disease(ASCVD)in the 2019 ESC/EAS guidelines were met by all patients.In the study,some laboratory assessments such as the gender,age,disease type,glycolipid,liver and kidney function as baseline data were recorded and compared between combination group and the single group.And basic treatments such as clopidogrel and(or)aspirin enteric-coated tablets,and β-receptor blockers were received by all patients.After 4weeks of continuous treatment in both groups,all patients’ glycolipid,liver and kidney function were examined in the outpatient,and the changes of blood lipid,LDL-C,Apo B and Lp(a)compared with the baseline,LDL-C reduction ≥50% from baseline,the compliance rate of LDL-C and the changes of related liver and kidney function indexes were recorded and compared between the two groups before and after the treatment.The incidence and severity of all adverse drug reaction events and the relevant safety of patients with extremely low LDL-C(LDL-C <0.78mmol/L(30mg/dl))were recorded.Results:1.The comparison of CHOL,TG,LDL-C,HDL-C between the two groups before treatment was not statistically significant(P>0.05).After 4 weeks of treatment,the two groups of CHOL,TG,LDL-C were significantly lower than before treatment(P<0.001),and the combination group CHOL,LDL-C decreased more significantly than the single group(P<0.001)There was no statistically significant difference between the two groups of TG after treatment(P>0.05).HDL-C in the combination group was lower than before treatment(P<0.001),and HDL-C in the single-agent group was higher than before treatment(P<0.001).HDL-C between the two groups was compared after 4 weeks of treatment,and the difference was statistically significant Significance(P<0.001).After 4weeks of treatment in the two groups,the median levels of LDL-C reduction from baseline were 63.5% and 25.3%,respectively.And the decrease in LDL-C from the baseline in the combination group was significantly higher than the decrease in LDL-C from the baseline in the single-agent group.Moreover,the difference between the two groups was statistically significant(Z=-7.257,P<0.001).After 4 weeks of treatment in the two groups,the compliance rate(90.2%)of LDL-C reduction of ≥50% from baseline in the combination group was significantly higher than that of the single-agent group(4.4%)of LDL-C reduction of ≥50% from baseline,and the difference between the two groups was statistically significant(P<0.001).2.The compliance rates of LDL-C<1.8mmol(70mg/d L),LDL-C<1.4mmol(55mg/d L),and LDL-C<0.78mmol(30mg/d L)in the combination group were 90.2%,75.6%,24.4%,respectively.The compliance rates of LDL-C<1.8mmol(70mg/d L),LDL-C<1.4mmol(55mg/d L),and LDL-C<0.78mmol(30mg/d L)in the single group were 22.2%,2.2%,and 0,respectively,and the difference between the two groups was statistically significant(P<0.001).3.The comparison of Apo B and Lp(a)between the two groups before treatment was not statistically significant(P>0.05).After 4 weeks of treatment,Apo B in the two groups decreased compared with before treatment(P<0.001),and the difference between the two groups of Apo B after 4 weeks of treatment was statistically significant(P<0.001).The Lp(a)of the combination group was significantly lower than that before treatment(P<0.001),and the Lp(a)of the single group had little change from before treatment,and the difference was not statistically significant(P>0.05).The Lp(a)between the two groups was compared after 4 weeks of treatment,and the difference was statistically significant(P<0.001).The Apo B reduction level(40.5%±17.8%)of the combination group was significantly higher than the baseline reduction level(20.1%±14.0%)of the single-agent group,and the difference between the two groups was statistically significant(P<0.001).The Lp(a)reduction level(38.3%±19.9%)of the combination group was significantly higher than the baseline Lp(a)reduction level(2.8%±19.6%)of the single group,and the difference between the two groups was statistically significant(P<0.001).4.The comparison of alanine aminotransferase(alanine aminotransferase,ALT),aspartate aminotransferase(aspartate aminotransferase,AST)、 serum creatinine(serum creatinine,Scr)、serum glucose(serum glucose,Glu)between the two groups before treatment was not statistically significant(P>0.05).After 4 weeks of treatment,the comparison of ALT,AST,Scr,Glu and other safety-related indicators between the two groups was not statistically significant(P>0.05),and the comparison of ALT,AST,Scr,Glu and other safety-related indicators between the same group was no statistical significance(P>0.05).Conclusion:1.For the extremely high-risk patients with ACS,on the basis of statins therapy,the combined use of PCSK9 inhibitors can achieve the effect of intensive lipid-lowering in the short term,suggesting that the extremely high-risk patients with ACS should be treated with PCSK9 inhibitors as soon as possible during hospitalization.2.Evolocumab has greater benefits in reducing Aop B and Lp(a)for patients at the extremely high-risk of ACS.3.PCSK9 inhibitor Evolocumab is safe and effective for the treatment of the extremely high-risk patients with ACS,which provides new ideas for the treatment of ACS.