title: Cardiovascular Safety in Drug Development: A Role for Endothelial Function Tests.
abstract: As drug development becomes a long and demanding process, it might also become a barrier to medical progress. Drug safety concerns are responsible for many of the resources consumed in launching a new drug. Despite the money and time expended on it, a significant number of drugs are withdrawn years or decades after being in the market. Cardiovascular toxicity is one of the major reasons for those late withdrawals, meaning that many patients are exposed to unexpected serious cardiovascular risks. It seems that current methods to assess cardiovascular safety are imperfect, so new approaches to avoid the exposure to those undesirable effects are quite necessary. Endothelial dysfunction is the earliest detectable pathophysiological abnormality, which leads to the development of atherosclerosis, and it is also an independent predictor for major cardiovascular events. Endothelial toxicity might be the culprit of the cardiovascular adverse effects observed with a significant number of drugs. In this article, we suggest the regular inclusion of the best validated and less invasive endothelial function tests in the clinical phases of drug development in order to facilitate the development of drugs with safer cardiovascular profiles.
authors.affiliation: Department of Cardiology, Hospital Universitario de Torrejon, Madrid, Spain Facultad de Ciencias Biosanitarias, Universidad Francisco de Vitoria, Madrid, Spain j.ruizgarcia@hotmail.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Ruiz-Garcia
authors.affiliation: Department of Cardiology, Hospital Universitario de Torrejon, Madrid, Spain Facultad de Ciencias Biosanitarias, Universidad Francisco de Vitoria, Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Alegria-Barrero
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D055808:Drug Discovery / Q000379:methods*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D061214:Patient Safety; D018570:Risk Assessment; D018675:Toxicity Tests / Q000379:methods*
keywords: atherosclerosis; cardiac pharmacology; endothelium; proarrhythmic effects