Celecoxib cardiovascular effects

Recent data suggest that COX-2 inhibitors, including rofe-coxib, valdecoxib, and celecoxib, may increase the risk for MI and stroke.47 There is also some evidence that the non-selective NSAIDs may increase the risk for cardiovascular events.47,48 Rofecoxib was withdrawn from the market in late 2004 because of safety concerns. The FDA requested the withdrawal of valdecoxib from the market in 2005. The FDA also asked the manufacturers of celecoxib and non-selective NSAIDs (prescription and over-the-counter) to include information about the potential adverse cardiovascular effects of these drugs in their product labeling. The cardiovascular risk with COX-2 inhibitors and NSAIDs may be greatest in patients with a history of, or with risk factors for, cardiovascular disease. The American Heart Association recommends that the use of COX-2 inhibitors be limited to low-dose, short-term therapy in patients for whom there is no appropriate alternative.48 Patients with cardiovascular disease should consult a clinician before using over-the-counter NSAIDs. 

Selectivity for COX-1 versus COX-2 is variable and incomplete for the older NSAIDs, but many selective COX-2 inhibitors have been synthesized. The selective COX-2 inhibitors do not affect platelet function at their usual doses. In testing using human whole blood, aspirin, ibuprofen, indomethacin, piroxicam, and sulindac are somewhat more effective in inhibiting COX-1. The efficacy of -2-selective drugs equals that of the older NSAIDs, while gastrointestinal safety may be improved. On the other hand, selective COX-2 inhibitors may increase the incidence of edema and hypertension. As of December 2008, celecoxib and the less selective meloxicam are the only COX-2 inhibitors marketed in the USA. Rofecoxib and valdecoxib, two previously marketed, selective COX-2 inhibitors, have been withdrawn from the market due to their association with increased cardiovascular thrombotic events. Celecoxib has an FDA-initiated "black box" warning concerning cardiovascular risks. It has been recommended that all NSAID product labels be revised to include cardiovascular risks. 

Solomon SD, Pfeffer MA, McMurray JJV, Fowler R, Finn P, Levin B, Eagle C, Hawk E, Lechuga M, Zauber AG. Bertagnolli MM, Arber N, Wittes J, ACP and PreSAPTrial Investigators. Effect of Celecoxib on Cardiovascular Events and Blood Pressure inTwoTriaIsfor the Prevention of Colorectal Adenomas. Circulation 2006 114 1028-1035... 

Solomon SD, Pfeffer MA, McMurray JJ et al. Effect of celecoxib on cardiovascular events and blood pressure in two trials for the prevention of colorectal adenomas. Circulation 2006 14 1028-1035. 

Johnson, A J., Hsu, Ai., Song, X., Lin, H.P., and Chen, C.S. (2002) The Cyclooxygenase-2 Inhibitor Celecoxib Perturbs Intracellular Calcium by Inhibiting Endoplasmic Reticulum Ca -ATPases. A Plausible Link with Its Antitumor Effect and Cardiovascular Risks, Biochem J. 366 (Pt 3), 831 37. 

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