The Role of PCSK9 Inhibitors in the Treatment of Hypercholesterolemia

Ann Pharmacother. 2018 Oct;52(10):1000-1018. doi: 10.1177/1060028018771670. Epub 2018 Apr 18.

Abstract

Objective: To evaluate the efficacy, safety, and cost-effectiveness of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors and describe its place in therapy for the treatment of hypercholesterolemia.

Data sources: A search of MEDLINE, CINAHL, and Clinicaltrials.gov was performed from January 2012 to March 2018 to identify literature pertaining to PCSK9 inhibitors using pre-specified search terms. Additional references were identified from citations of the literature.

Study selection and data extraction: Only articles in English were reviewed. Phase II, phase III, pooled, post hoc, and cardiovascular (CV) trials were included. Cost-effectiveness studies and conference materials were also reviewed.

Data synthesis: All trials evaluating alirocumab and evolocumab demonstrated significant low-density lipoprotein cholesterol (LDL-C) lowering versus comparators. Two trials revealed a decrease in the major adverse cardiovascular events (MACE) end point with PCSK9 inhibitor use; 1 of these 2 trials revealed a decrease in all-cause mortality with alirocumab use. No significant safety concerns apart from injection site reactions were noted. Despite these results, 4 cost-effectiveness analyses failed to meet acceptable thresholds. Relevance to Patient Care and Clinical Practice: This review describes the most up-to-date evidence regarding PCSK9 inhibitors. A discussion on LDL-C lowering potential, effect on CV events and mortality, safety considerations, feasibility of administration, and cost are included to guide clinicians on future use.

Conclusion: The PCSK9 inhibitor drug class is an effective LDL-C lowering option for patients with the highest risk of CVD events and high LDL-C despite the use of statin therapy. For more widespread use, significant cost reductions are needed.

Keywords: ambulatory care; cholesterol; clinical practice; dyslipidemia; hypercholesterolemia; outcomes.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Anticholesteremic Agents / therapeutic use*
  • Cholesterol, LDL / blood
  • Clinical Trials as Topic / statistics & numerical data
  • Cost-Benefit Analysis
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy*
  • PCSK9 Inhibitors*
  • Practice Patterns, Physicians' / statistics & numerical data

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Anticholesteremic Agents
  • Cholesterol, LDL
  • Enzyme Inhibitors
  • PCSK9 Inhibitors
  • PCSK9 protein, human
  • evolocumab
  • alirocumab