前蛋白转化酶枯草溶菌素9抑制剂在不稳定型心绞痛药物球囊介入治疗后的应用

Application of proprotein convertase subtilisin/kexin type 9 inhibitor after drug balloon intervention for unstable angina pectoris

目的观察不稳定型心绞痛患者药物球囊介入治疗后应用前蛋白转化酶枯草溶菌素9(PCSK9)抑制剂治疗的效果及安全性。方法2021年1月-2022年1月阜外华中心血管病医院诊治不稳定型心绞痛患者280例,随机分为观察组和对照组各140例,均行药物球囊介入治疗。术后对照组给予瑞舒伐他汀(10 mg/次,1次/d,口服)治疗,观察组在对照组基础上联合PCSK9抑制剂依洛尤单抗(140 mg/次,1次/2周,皮下注射)治疗。治疗前、治疗12个月时,检测血脂水平;行血管内超声检查,记录治疗后最小管腔面积。治疗12个月时评价疗效,观察主要心血管不良事件发生情况。结果观察组治疗后最小管腔面积[(4.89±0.92)mm^(2)]大于对照组[(4.15±0.82)mm^(2)](t=7.105,P<0.001)。治疗前观察组TC[(4.50±1.20)mmol/L]、TG[(2.12±0.54)mmol/L]、LDL-C[(2.76±0.76)mmol/L]、HDL-C[(1.13±0.24)mmol/L]、Lp(a)[(320.20±76.33)mg/L]、apoA[(1.32±0.34)g/L]、apoB[(1.04±0.22)g/L]水平与对照组[(4.43±1.12)mmol/L、(2.14±0.51)mmol/L、(2.72±0.71)mmol/L、(1.12±0.21)mmol/L、(328.18±74.45)mg/L、(1.31±0.28)g/L、(1.03±0.20)g/L]比较差异均无统计学意义(t=0.505、-0.319、0.455、0.371、-0.886、0.269、0.398,P均>0.05);治疗12个月时观察组TC[(3.34±1.01)mmol/L]、TG[(1.30±0.38)mmol/L]、LDL-C[(1.59±0.27)mmol/L]、Lp(a)[(199.45±75.50)mg/L]、apoB[(0.65±0.19)g/L]水平均低于对照组[(3.78±0.98)mmol/L、(1.66±0.34)mmol/L、(1.80±0.26)mmol/L、(231.10±76.62)mg/L、(0.78±0.17)g/L](t=-3.699、-8.354、-6.629、-3.481、-6.033,P均<0.05),HDL-C[(1.27±0.24)mmol/L]、apoA[(1.53±0.34)g/L]水平均高于对照组[(1.17±0.17)mmol/L、(1.36±0.31)g/L](t=4.023,P<0.001;t=4.372,P<0.001);2组治疗12个月时TC、TG、LDL-C、Lp(a)、apoB水平均低于治疗前(P<0.05),HDL-C、apoA水平均高于治疗前(P<0.05)。观察组治疗总有效率(95.7%)高于对照组(85.7%)(χ^(2)=2.633,P=0.008),主要心血管不良事件发生率(2.9%)低于对照组(10.7%)(χ^(2)=6.832,P=0.009)。结论不稳定型心绞痛患者药物球囊介入治疗后在他汀类药物基础上联合PCSK9抑制剂治疗可明显改善临床症状,降低血脂水平,减少主要心血管不良事件发生。

Objective To observe the efficacy and safety of proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitor after drug balloon intervention in patients with unstable angina pectoris(UAP).Methods From January 2021to January 2022,280 patients with UAP received drug balloon intervention in Fuwai Central China Cardiovascular Hospital,and were randomly and equally divided into observation group and control group.After operation,control group was given rosuvastatin orally(10 mg,once a day),and observation group was subcutaneously injected with PCSK9inhibitor ilozumab(140 mg,once two weeks)besides the treatment in control group.The blood lipid levels were detected before and after 12-month treatment.Intravascular ultrasound was performed to record the minimal lumen area after treatment.The efficacy was evaluated after 12-month treatment,and the occurrence of major cardiovascular adverse events was observed.Results The minimal lumen area was larger in observation group[(4.89±0.92)mm^(2)]than that in control group[(4.15±0.82)mm^(2)]after treatment(t=7.105,P<0.001).The levels of total cholesterol(TC),triacylglycerol(TG),low-denisity lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),lipoprotein(a)[Lp(a)],apolipoprotein(apo)A and apoB showed no significant differences before treatment between observation group[(4.50±1.20)mmol/L,(2.12±0.54)mmol/L,(2.76±0.76)mmol/L,(1.13±0.24)mmol/L,(320.20±76.33)mg/L,(1.32±0.34)g/L,(1.04±0.22)g/L]and control group[(4.43±1.12)mmol/L,(2.14±0.51)mmol/L,(2.72±0.71)mmol/L,(1.12±0.21)mmol/L,(328.18±74.45)mg/L,(1.31±0.28)g/L,(1.03±0.20)g/L](t=0.505,-0.319,0.455,0.371,-0.886,0.269,0.398;all P values>0.05).After-12 month treatment,the levels of TC,TG,LDL-C,Lp(a)and apoB were lower in observation group[(3.34±1.01)mmol/L,(1.30±0.38)mmol/L,(1.59±0.27)mmol/L,(199.45±75.50)mg/L,(0.65±0.19 g/L)]than those in control group[(3.78±0.98)mmol/L,(1.66±0.34)mmol/L,(1.80±0.26)mmol/L,(231.10±76.62)mg/L,(0.78±0.17)g/L](t=-3.699,-8.354,-6.629,-3.481,-6.033;all P values>0.05),and the levels of HDL-C and apo A were higher in observation group[(1.27±0.24)mmol/L,(1.53±0.34)g/L]than those in control group[(1.17±0.17)mmol/L,(1.36±0.31)g/L](t=4.023,P<0.001;t=4.372,P<0.001).The levels of TC,TG,LDL-C,Lp(a)and apoB were lower after 12-month treatment than those before treatment in two groups(P<0.05),and the levels of HDL-C and apoA were higher after 12-month treatment than those before treatment(P<0.05).The total effective rate was higher in observation group(95.7%)than that in control group(85.7%)(χ^(2)=2.633,P=0.008),and the incidence of major cardiovascular adverse events was lower in observation group(2.9%)than that in control group(10.7%)(χ^(2)=6.832,P=0.009).Conclusion In patients with UAP,the application of PCSK9 inhibitors on the basis of statin can significantly alleviate the clinical symptoms,lower the lipid levels,and reduce the occurrence of major cardiovascular adverse events after drug balloon intervention.