Relatively little new information on the two recently marketed selective Cox-2 inhibitors emerged. Gregory Bell (Merck & Co) presented rofecoxib experiences. Its efficacy was comparable to that of strong classical NSAIDs; gastrointestinal symptoms were close to but not identical to those induced by placebo. Discontinuation of therapy in trials was also intermediate. It is known that close to 5% of patients develop edema and this has led to careful monitoring of renal function. No change in glomerular filtration rate occurred over 12 months of exposure in clinical trials, mostly in osteoarthritis (OA). Radiographic data showed no difference between diclofenac and rofecoxib. There were no data on any influence on progression of spur formation in OA. Importantly, low dose aspirin for cardiovascular disease was excluded in these trials.
Celecoxib data were reported by John Fort (Searle, Skokie, IL, USA). This drug has been dispensed in 9 million prescriptions in the USA, corresponding to perhaps 30% of new NSAID prescriptions, so far without major reports regarding adverse reactions. The dose of 10 0mg twice daily was not superior to 200 mg daily. It also appears that a dose of 400 mg daily was not more potent than 200 mg; however, the higher dose caused more adverse reactions.
Perry Halushka (Medical University of South Carolina, Charleston, SC, USA) drew attention to the potential risk of TX-related vascular occlusion after selective Cox-2 inhibition, and illustrated this with a couple of case reports. One patient suffering from scleroderma had developed pulmonary embolism after 2-4 doses of a Cox-2 inhibitor and her TXA2 concentration was four times normal. Patients with an antiphospholipid syndrome may also be at risk, and vascular occlusions have been seen in connection with celecoxib therapy. On the other hand, patients with a tendency to bleed, such as those with hemophilia, have not been exposed to selective Cox-2 inhibitors.
Addressing the question of the cardiovascular safety of celecoxib, Robert Makuch (Yale University, New Haven, CT, USA) had analysed data in Searle's database of 13 000 patient records from 2-24 weeks of placebo controlled trials as well as records for 6000 patients in a two year open label trial of celecoxib safety. No increased risk for myocardial infarct or any serious vascular event emerged from this investigation.