Related Experiment Video

Updated: Dec 17, 2025

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
08:14

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9

Published on: August 28, 2018

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Serious adverse events and deaths in PCSK9 inhibitor trials reported on ClinicalTrials.gov: a systematic review

F H van Bruggen1, G B J Nijhuis1, S U Zuidema1

  • 1University of Groningen, University Medical Center Groningen, Department of General Practice and Elderly Care Medicine , Groningen, The Netherlands.

Expert Review of Clinical Pharmacology
|June 30, 2020
PubMed
Abstract

Insights

PCSK9 inhibitors did not improve cardiovascular health in trials. Evolocumab, a PCSK9 inhibitor, was associated with an increased risk of all-cause mortality, necessitating further investigation.

Area of Science:

  • Cardiovascular Medicine
  • Pharmacology

Background:

  • Previous reviews on PCSK9 inhibitors focused on composite outcomes.
  • ClinicalTrials.gov offers data on individual clinical outcomes.

Purpose of the Study:

  • To assess PCSK9 inhibitors' effect on myocardial infarction, stroke/TIA, heart failure, diabetes, neurocognitive events, SAEs, and deaths.
  • To analyze individual clinical outcomes registered on ClinicalTrials.gov.

Main Methods:

  • Systematic review of randomized trials comparing PCSK9 inhibitors with placebo.
  • Searched PubMed, regulatory reports, ClinicalTrials.gov, and company websites.
  • Collected data on study characteristics, risk of bias, and participant outcomes.

Main Results:

  • 33 lipid-lowering and 4 clinical outcomes trials identified (n=16,958 and n=73,836).
  • High risk of bias noted in studies.
  • PCSK9 inhibitors did not impact investigated outcomes; however, alirocumab reduced SAEs, and evolocumab possibly increased mortality.

Conclusions:

  • Meta-analysis of ClinicalTrials.gov data indicates PCSK9 inhibitors do not enhance cardiovascular health.
  • Evolocumab use was linked to a higher risk of all-cause mortality.
Keywords:
Adverse eventsClinicalTrials.govPCSK9 inhibitorsall-cause mortalityreview

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