Background: Whether nonsteroidal anti-inflammatory drugs (NSAIDs) increase cardiovascular risk has been debated since the withdrawal of rofecoxib from the U.S. market. NSAIDs can cause fluid retention, with potential implications for patients with chronic heart failure. The American Heart Association has recommended that NSAIDs be avoided when possible in patients with established or increased risk of cardiovascular disease. Nevertheless, the wide availability of nonprescription NSAIDs may lead to the perception that these agents are safer than they actually are. Gislason and colleagues studied the risk of death and hospitalization because of acute myocardial infarction (MI) and heart failure associated with use of NSAIDS.

The Study: The study coordinators conducted a retrospective cohort study of 107,092 Danish patients who survived their first hospitalization caused by heart failure, and reviewed their status for up to nine years to see whether they died or were subsequently hospitalized for heart failure or MI. The use of NSAIDs after the initial hospitalization was monitored through pharmacy registries. Exposure to NSAIDs was then used to estimate risk of death or rehospitalization using Cox proportional hazards regression models.

Results: During the study, 56.9 percent of the cohort died. Of the original cohort, 33.9 percent received at least one prescription for an NSAID after their initial hospitalization, with mean duration of treatment ranging from 42 days with rofecoxib, to 97 days with ibuprofen. NSAIDs were associated with a dose-dependent increased risk of rehospitalization and death, especially rofecoxib, celecoxib (Celebrex), and diclofenac (Voltaren; see accompanying table). No increase in mortality occurred with low dosages of ibuprofen (up to 1,200 mg per day) or naproxen (Naprosyn; up to 500 mg per day), although it was observed with higher dosages. Selective and nonselective NSAIDs were associated with a greater risk of rehospitalization for heart failure or MI. Hazard ratios for MI were similar for all NSAIDs, although the highest risk of MI occurred with rofecoxib and diclofenac. Rofecoxib was also associated with the highest risk of heart failure.

Conclusion: Selective and nonselective NSAIDs are associated with increased mortality and cardiovascular morbidity, with a generally dose-dependent response. Patients with chronic heart failure should avoid using NSAIDs whenever possible. Patients who require these drugs should use NSAIDs, such as ibuprofen or naproxen, in the lowest dosage and for the shortest time possible.