title: Cardiovascular hazard and non-steroidal anti-inflammatory drugs.
abstract: Selective inhibitors of cyclooxygenase (COX)-2 depress prostacyclin (PGI(2)) without a concomitant inhibition of platelet COX-1-derived thromboxane (Tx)A(2). Experiments in gene-deleted mice have shown that ablation of the PGI(2) receptor (the IP) predisposes to an exaggerated response to agonists which elevate blood pressure, accelerate atherogenesis and induce thrombosis. Such a class-based effect would be expected to be modulated by the underlying risk of cardiovascular disease in patients, elements of drug exposure, such as dose, duration of action and duration of dosing, and inter-individual variability of drug response. Five placebo-controlled trials of three structurally distinct selective inhibitors of COX-2 have revealed an increased hazard of myocardial infarction and stroke consistent with a mechanism-based class-specific cardiovascular hazard. Sustained inhibition of platelet TxA(2) by aspirin affords cardiovascular benefit, despite concomitant inhibition of PGI(2). Although there is no information from randomized placebo-controlled trials, traditional non-steroidal anti-inflammatory drugs, such as naproxen, dicofenac and ibuprofen, might differ in their effects of cardiovascular biology.
authors.affiliation: Institute for Translational Medicine and Therapeutics and the Department of Pharmacology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Dairong
authors.initials: D
authors.lastname: Wang
authors.forename: Dairong
authors.initials: D
authors.lastname: Wong
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Garret A
authors.initials: GA
authors.lastname: Fitzgerald
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000378:metabolism; D006801:Humans; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal