Reiner Željko
a University Hospital Centre Zagreb, School of Medicine University of Zagreb, Department of Internal Medicine , Kispaticeva 12, Zagreb, Croatia +385 1 237 6041 ; +385 1 238 8623 ;
Expert Opin Drug Metab Toxicol. 2015;11(10):1517-21. doi: 10.1517/17425255.2015.1075506. Epub 2015 Sep 2.
Lowering low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular disease (CVD) morbidity and mortality. Statins are the treatment of choice for lowering LDL-C but a considerable number of patients treated with statins are unable to achieve LDL-C target values and many are statin-intolerant. New LDL-C-lowering drugs--antibodies to PCSK9 (alirocumab, evolocumab and bococizumab)--have been developed and are being tested in large clinical trials. They further reduce LDL-C above maximally tolerated statin therapy by up to > 70%; they also reduce Lp(a), non-HDL-C, apolipoprotein-B, and modestly increase HDL-C. These drugs are well tolerated and even patients who achieved very low LDL-C ≤ 0.65 mmol/l (∼ 25 mg/dl) did not have any significant adverse effects. Treatment with PCSK9 inhibitors resulted in LDL-C target values in 70-90% of patients according to the guidelines. However, although PCSK9 inhibitors seem to be the most promising emerging therapeutic option for LDL-C lowering today, outcome data with endpoints on their effects are still lacking. Another important open question is their long-term safety. Their use in statin-intolerant patients also raises questions, as the criteria for statin-intolerance are neither clear nor generally accepted. The presumed high cost of PCSK9 inhibitors might be an obstacle for their broader use.
降低低密度脂蛋白胆固醇（LDL-C）可降低心血管疾病（CVD）的发病率和死亡率。他汀类药物是降低LDL-C的首选治疗药物，但相当一部分接受他汀类药物治疗的患者无法达到LDL-C目标值，且许多患者对他汀类药物不耐受。新型降低LDL-C的药物——抗PCSK9抗体（阿利西尤单抗、依洛尤单抗和博考西单抗）——已被研发出来，并正在大型临床试验中进行测试。它们在最大耐受剂量他汀类药物治疗的基础上，可进一步将LDL-C降低多达>70%；它们还可降低脂蛋白（a）、非HDL-C、载脂蛋白B，并适度升高HDL-C。这些药物耐受性良好，即使是LDL-C极低≤0.65 mmol/L（约25 mg/dl）的患者也没有任何明显的不良反应。根据指南，使用PCSK9抑制剂治疗可使70-90%的患者达到LDL-C目标值。然而，尽管PCSK9抑制剂似乎是目前降低LDL-C最有前景的新兴治疗选择，但仍缺乏关于其疗效终点的结果数据。另一个重要的未解决问题是它们的长期安全性。它们在他汀类药物不耐受患者中的使用也引发了问题，因为他汀类药物不耐受的标准既不明确，也未被普遍接受。PCSK9抑制剂的高昂成本可能是其更广泛应用的障碍。
