Open AccessImproving Assessment of Drug Safety Through Proteomics
Author(s) -
Stephen Williams,
Ashwin Murthy,
Robert Kirk DeLisle,
Craig Hyde,
Anders Mälarstig,
Rachel Ostroff,
Sophie Weiss,
Mark R. Segal,
Patricia A. Ganz
Publication year - 2018
Publication title -
circulation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.795
H-Index - 607
eISSN - 1524-4539
pISSN - 0009-7322
DOI - 10.1161/circulationaha.117.028213
Subject(s) - medicine , myocardial infarction , adverse effect , stroke (engine) , drug , pharmacology , cardiology , bioinformatics , mechanical engineering , engineering , biology
Early detection of adverse effects of novel therapies and understanding of their mechanisms could improve the safety and efficiency of drug development. We have retrospectively applied large-scale proteomics to blood samples from ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events), a trial of torcetrapib (a cholesterol ester transfer protein inhibitor), that involved 15 067 participants at high cardiovascular risk. ILLUMINATE was terminated at a median of 550 days because of significant absolute increases of 1.2% in cardiovascular events and 0.4% in mortality with torcetrapib. The aims of our analysis were to determine whether a proteomic analysis might reveal biological mechanisms responsible for these harmful effects and whether harmful effects of torcetrapib could have been detected early in the ILLUMINATE trial with proteomics.