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Recent Updates on the Use of PCSK9 Inhibitors in Patients with Atherosclerotic Cardiovascular Disease

  • Dave L. DixonEmail author
  • Lauren G. Pamulapati
  • John D. Bucheit
  • Evan M. Sisson
  • Shawn R. Smith
  • Caroline J. Kim
  • George F. Wohlford
  • Jonah Pozen
Coronary Heart Disease (S. Virani and S. Naderi, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Coronary Heart Disease

Abstract

Purpose of Review

Atherosclerotic cardiovascular disease (ASCVD) is caused by elevated levels of low-density lipoprotein cholesterol (LDL-C). Although statins significantly reduce ASCVD risk, there remains a high degree of residual risk in statin-treated patients. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition has emerged as a significant therapeutic target for further lowering of LDL-C when used in combination with statins. The purpose of this review is to provide an update on recent evidence supporting the use of PCSK9 inhibitors in patients with ASCVD.

Recent Findings

Alirocumab and evolocumab were approved by the US Food and Drug Administration in 2015. Multiple phase II and III studies have demonstrated that these agents reduce LDL-C levels by up to 60% and are relatively safe, with the exception of injection site reactions. Additionally, two randomized controlled clinical trials have demonstrated that both alirocumab and evolocumab reduce ASCVD events when used in combination with statin therapy compared to statin alone. In light of this evidence, the 2018 Cholesterol Guideline incorporated PCSK9 inhibitors into the treatment algorithm for select secondary prevention patients unable to achieve an LDL-C below 70 mg/dL despite maximally tolerated statin plus ezetimibe.

Summary

Although PCSK9 inhibitors provide substantial reductions in LDL-C levels and reduce ASCVD events in secondary prevention populations, the cost-effectiveness of alirocumab and evolocumab limit widespread use. Additional research is needed to explore the role of PCSK9 inhibitors in other populations, including primary prevention, patients unable to tolerate statins, and acute myocardial infarction.

Keywords

PCSK9 Alirocumab Evolocumab Dyslipidemia Low-density lipoprotein cholesterol Cardiovascular disease 

Notes

Compliance with Ethical Standards

Conflict of Interest

Dave L. Dixon, Lauren G. Pamulapati, John Bucheit, Evan M. Sisson, Shawn R. Smith, Caroline Kim, George F. Wohlford, and Jonah Pozen declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Dave L. Dixon
    • 1
    Email author
  • Lauren G. Pamulapati
    • 1
  • John D. Bucheit
    • 1
  • Evan M. Sisson
    • 1
  • Shawn R. Smith
    • 1
  • Caroline J. Kim
    • 1
  • George F. Wohlford
    • 1
  • Jonah Pozen
    • 2
  1. 1.Department of Pharmacotherapy & Outcomes ScienceVirginia Commonwealth University School of PharmacyRichmondUSA
  2. 2.Division of Cardiology, Internal MedicineVirginia Commonwealth University Health SystemRichmondUSA

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