DALLAS – The use of NSAIDs–whether cyclooxygenase-2-selective or not–in patients who've had an acute MI increases their risk of death, especially in higher doses, according to data from the Danish National Patient Registry.
To patients with ischemic heart disease, “I would say that you should try to avoid these drugs, but if you need to take them, use lower doses,” Dr. Gunnar H. Gislason said at the annual scientific sessions of the American Heart Association.
The widely publicized prior studies that revealed the increased risks of MI and death associated with NSAID use–and that resulted in some COX-2-selective agents being taken off the market as well as an across-the-board black box label warning for all NSAIDs–were based largely on patient populations with an average background cardiovascular risk. Dr. Gislason and his coinvestigators sought to learn whether the increased cardiovascular risk associated with NSAID use also applied to patients at very high cardiovascular risk: namely, those who've already had an MI. Funding for their study was provided by the Danish Heart Foundation.
Dr. Gislason reported on all 58,432 patients discharged from Danish hospitals following a first acute MI during 1995-2002. A centralized national prescription database revealed that more than 40% of these first-MI survivors subsequently filled at least one prescription for an NSAID. Nearly 10% of all patients used a COX-2 inhibitor after having their MI.
The two most widely used, older, nonselective NSAIDs in Denmark are ibuprofen (used by 17.5% of the post-MI patients), and diclofenac (used by 10.6%). Rofecoxib was taken by 5.2% of the patients, whereas celecoxib was used by 4.3%.
The use of a COX-2 inhibitor in high doses–that is, more than 25 mg/day for rofecoxib or 200 mg of celecoxib–was associated with a four- to fivefold increased mortality risk during the time a patient was on the drug, compared with NSAID nonusers. Lower-dose therapy with a COX-2 inhibitor was associated with a lesser–albeit significantly increased–mortality risk. (See box.) The risk calculations were adjusted for comorbid illnesses, age, gender, and socioeconomic status, according to Dr. Gislason of Bispebjerg University Hospital, Copenhagen.
High-dose therapy with the nonselective NSAIDs was also associated with increased mortality risk.
The rate of out-of-hospital deaths was unusually high in the NSAID users. The Danish investigators are still sorting out the causes using death certificate data. One possibility, as yet unconfirmed, is that NSAID users experienced an excess of arrhythmic deaths outside the hospital. In addition, hospitalization for heart failure following an MI was more common among users of COX-2 inhibitors.
