Cyclooxygenase-2 (COX-2) inhibiting drugs were developed to provide the anti-inflammatory effects of nonsteroidal anti-inflammatory drugs (NSAIDs) with a reduced risk of gastrointestinal bleeding. Concerns have arisen that COX-2 inhibitors could have cardiovascular and renal adverse effects similar to those of nonselective NSAIDs, such as raised systemic vascular resistance and decreased renal perfusion. The result could be an increase in congestive cardiac failure in susceptible patients. Mamdani and colleagues used databases on prescription drugs and hospital admissions in a Canadian province to look for any association between COX-2 inhibitor use and hospital admission for congestive cardiac failure.
From a total population of 1.3 million persons aged 65 years or older, the investigators identified patients who were prescribed COX-2 inhibitors (rofecoxib and celecoxib) or nonselective NSAIDs from April 2000 through March 2001. Using the databases for previous prescriptions, they identified 14,583 NSAID-naïve persons who started rofecoxib therapy and 18,908 NSAID-naïve persons who started celecoxib therapy. There were 5,391 first-time users of nonselective NSAIDs (predominately diclofenac plus misoprostol, naproxen, or ibuprofen). These groups of patients were compared for admission to hospital because of heart failure with 100,000 control patients who represented the non-NSAID users in the population age group.
The two groups using COX-2 inhibitors were comparable. For example, compared with the NSAID users and control subjects, the patients using COX-2 inhibitors were more likely to be female, to have had echocardiography, and to have received loop diuretics, digoxin, and several cardiac drugs, including beta blockers, calcium channel antagonists, and angiotensin-converting enzyme inhibitors. During the study, 654 patients were admitted to a hospital for treatment of congestive heart failure. The rate of admission was significantly increased for those receiving rofecoxib and NSAID compared with the control group but was not increased for celecoxib users. The risk of hospital admission was significantly increased in those receiving rofecoxib compared with those receiving NSAIDs. The increased risk in those receiving rofecoxib also was noted in the subgroup of patients with no history of a heart-failure–related hospital admission.
The authors conclude that rofecoxib and nonselective NSAID use is associated with an increased risk of hospital admission for congestive heart failure, but celecoxib use is not. These results are consistent with studies showing more marked changes in blood pressure and edema with rofecoxib and could be related to the longer half-life and other pharmacokinetic properties of this drug. They call for further studies to clarify this potentially important effect of medications commonly prescribed for elderly patients.