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心脏移植后患者应用 PCSK9 抑制剂治疗高胆固醇血症。

Treatment of hypercholesterolaemia with PCSK9 inhibitors in patients after cardiac transplantation.

机构信息

Department of Cardiac Surgery, University of Leipzig-Leipzig Heart Center, Leipzig, Germany.

Department of Cardiology / Rhythmology, University of Leipzig-Leipzig Heart Center, Leipzig, Germany.

出版信息

PLoS One. 2019 Jan 16;14(1):e0210373. doi: 10.1371/journal.pone.0210373. eCollection 2019.

Abstract

BACKGROUND

Hypercholesterolaemia is common in patients after cardiac transplantation. Monoclonal antibodies that inhibit proprotein convertase subtilisin-kexin type 9 (PCSK9) reduce low-density lipoprotein (LDL) cholesterol levels and subsequently the risk of cardiovascular events in patients with dyslipidaemia. There are no published data on the effect of this medication class on cholesterol levels in patients after cardiac transplantation.

METHODS

In this retrospective study we investigated patients who were treated with PCSK9 inhibitors either because of intolerance of statins or residual hypercholesterolaemia with evidence of cardiac allograft vasculopathy. We compared the data of patients prior to the start with these medications with their most recent dataset.

RESULTS

Ten patients (nine men; mean age 58±6 years) underwent cardiac transplantation 8.3±4.5 (range 3-15) years ago. The treatment duration of Evolocumab or Alirocumab was on average 296±125 days and lead to a reduction of total Cholesterol (281±52 mg/dl to 197±36 mg/dl; p = 0.002) and LDL Cholesterol (170±22 mg/dl to 101±39 mg/dl; p = 0.001). No significant effects on HDL Cholesterol, BNP, Creatin Kinase or hepatic enzymes were noticed. There were no unplanned hospitalisations, episodes of rejections, change of ejection fraction or opportunistic infections. Both patients on Alirocumab developed liver pathologies: One patient died of hepatocellular carcinoma and the other developed hepatitis E.

CONCLUSIONS

Our study demonstrates that the PCSK9 inhibitors Evolocumab and Alirocumab lead to a significant reduction of LDL Cholesterol in heart transplantation recipients. No effect on cardiac function or episodes of rejections were noticed. Larger and long-term studies are needed to establish safety and efficacy of PCSK9 inhibitors after cardiac transplantation.

摘要

背景

心脏移植后患者常出现高胆固醇血症。抑制脯氨酰肽链内切酶枯草溶菌素/克那霉 9(PCSK9)的单克隆抗体可降低低密度脂蛋白(LDL)胆固醇水平,从而降低血脂异常患者发生心血管事件的风险。目前尚无关于此类药物对心脏移植后患者胆固醇水平影响的发表数据。

方法

在这项回顾性研究中,我们调查了因他汀类药物不耐受或存在心脏移植后血管病且有残余高胆固醇血症证据而接受 PCSK9 抑制剂治疗的患者。我们比较了这些患者开始使用这些药物之前和最近的数据。

结果

10 名患者(9 名男性;平均年龄 58±6 岁)在 8.3±4.5(3-15)年前接受了心脏移植。依洛尤单抗或阿利西尤单抗的治疗时间平均为 296±125 天,导致总胆固醇(281±52 mg/dl 降至 197±36 mg/dl;p=0.002)和 LDL 胆固醇(170±22 mg/dl 降至 101±39 mg/dl;p=0.001)降低。高密度脂蛋白胆固醇、BNP、肌酸激酶或肝酶无显著变化。未发生计划外住院、排斥反应发作、射血分数改变或机会性感染。接受阿利西尤单抗治疗的两名患者均出现肝脏病变:一名患者死于肝细胞癌,另一名患者发生戊型肝炎。

结论

我们的研究表明,PCSK9 抑制剂依洛尤单抗和阿利西尤单抗可显著降低心脏移植受者的 LDL 胆固醇。未观察到对心功能或排斥反应发作的影响。需要更大规模和长期的研究来确定心脏移植后 PCSK9 抑制剂的安全性和疗效。

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