Emotion recollected in tranquility: lessons learned from the COX-2 saga.
Nonsteroidal antinflammatory drugs (NSAIDs) inhibit prostaglandin formation by cyclooxygenases (COX) 1 and 2. NSAIDs selective for inhibition of COX-2 are less likely than traditional drugs to cause serious gastrointestinal adverse effects, but predispose to adverse cardiovascular events, such as heart failure, myocardial infarction, and stroke. Evidence from human pharmacology and genetics, genetically manipulated rodents, and other animal models and randomized trials indicates that this is consequent to suppression of COX-2-dependent cardioprotective prostagladins, particularly prostacyclin. Lessons drawn from how this saga unfolded are relevant to how we approach drug surveillance and regulation, integrate diversifed forms of information and might pursue a more personalized approach to drug efficacy and risk.
Grosser
Tilo
T
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6084, USA. garret@upenn.edu
Yu
Ying
Y
Fitzgerald
Garret A
GA
D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology*; D051545:Cyclooxygenase 1 / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D011358:Product Surveillance, Postmarketing; D018570:Risk Assessment
D052246:Cyclooxygenase 2 Inhibitors; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2