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Year : 2017  |  Volume : 6  |  Issue : 1  |  Page : 12-17

Proprotein convertase subtilisin kexin 9 inhibitors: Current status and future directions

1 Chairman, Department of Cardiology, Dharma Vira Heart Center, Sir Ganga Ram Hospital, New Delhi, India
2 Senior Resident, Department of Cardiology, G. B. Pant Hospital, New Delhi, India

Correspondence Address:
JPS Sawhney
Department of Cardiology, Dharma Vira Heart Center, Sir Ganga Ram Hospital, New Delhi - 110 060
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2250-3528.196649

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The discovery of proprotein convertase subtilisin kexin 9 (PCSK9) has considerably changed the therapeutic options in the field of lipid management. PCSK9 reduces low-density lipoprotein receptor (LDLR) recycling, leading to a decrease of LDL cholesterol (LDL-C) receptors on the surface of hepatocytes and a subsequent increase of circulating LDL-C levels. Among the various approaches to PCSK9 inhibition, human data are only available for inhibition of PCSK9 binding to LDLR by monoclonal antibodies. In Phase II studies, the two most advanced monoclonal antibodies in development (alirocumab and evolocumab) decreased atherogenic lipoproteins very effectively and were well tolerated. Sixty percent to seventy percent of reduction in LDL-C was observed, especially when subcutaneous injections were performed regularly every 2 weeks. No significant side effects were observed, with the exception of injection-site reactions. Three large Phase III programs with the new anti-PCSK9 antibodies are currently underway in patients with acute coronary syndrome and LDL-C inadequately controlled by standard treatments. In this review, we will discuss the effect of PCSK9 inhibition, its current status, and future perspectives.

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