The risk of death and recurrent congestive heart failure was higher in elderly patients prescribed non-steroidal anti-inflammatory drugs (NSAIDs) or rofecoxib than in those prescribed celecoxib. In pairwise analysis, we found similar risks of death and recurrent congestive heart failure in patients prescribed rofecoxib or NSAIDs.
An association between cyclo-oxygenase-2 inhibitors and congestive heart failure is emerging, but there seem to be intra-class differences. Case reports have shown worsening heart failure associated with cyclo-oxygenase-2 inhibitors,45
and data from a small prospective database for disease management suggests that patients who are prescribed a cyclo-oxygenase-2 inhibitor on discharge are more likely to be readmitted for congestive heart failure within a year compared with those not prescribed a cyclo-oxygenase-2 inhibitor (32.5% versus 22.0%, respectively, P < 0.05).46
In that study, the risk of recurrent congestive heart failure differed between rofecoxib and celecoxib (35.5% versus 32.5%, respectively). In a drug safety database, rofecoxib was associated with significantly more reports of cardiac failure than celecoxib.24
Similarly, in a large, population based study of stable hypertensive patients with no history of heart failure, those who were newly treated with rofecoxib were significantly more likely than those newly treated with celecoxib to have a diagnosis of heart failure as an outpatient (rate ratio 1.26, 95% confidence interval 1.06 to 1.48) and as an inpatient (1.52, 1.15 to 2.02).47
In that study, the rates of heart failure were similar between the celecoxib and NSAIDs groups. Finally, in a recent population based study of cyclo-oxygenase-2 inhibitors and congestive heart failure, users of rofecoxib and NSAIDs, but not celecoxib, had a higher risk of admission for congestive heart failure than controls receiving non-NSAIDs.36
Findings were similar in a subgroup analysis of patients with a history of admission for congestive heart failure. In pairwise comparisons, they found a significantly higher risk of admission for congestive heart failure in patients prescribed rofecoxib than in those prescribed celecoxib or NSAIDs (adjusted rate ratio 1.8, 95% confidence interval 1.4 to 2.4 and 1.5, 1.1 to 2.1).
Our findings are consistent with these data and are unique because we studied high risk patients with known congestive heart failure and we found a lower risk of death, assessed alone and in combination with recurrent congestive heart failure, in patients prescribed celecoxib compared with those prescribed NSAIDs or rofecoxib. Our data show that celecoxib may be safer than NSAIDs in high risk patients and that there may be important differences between cyclo-oxygenase-2 inhibitors. Differences in selectivity48
may, at least in part, explain the different results observed in patients prescribed celecoxib compared with those prescribed rofecoxib. NSAIDs also show differences in selectivity. The number of patients prescribed NSAIDs in our study was, however, small so we grouped the NSAIDs. The relative side effects of individual NSAIDs in congestive heart failure remain unknown.
Our study has several limitations. Firstly, patients who were classified as not taking drugs may have been using over the counter aminosalicylic acid or ibuprofen. In 2000, Santé Québec, a government public health agency, estimated that 17.0% and 2.2% of people aged 65 or more bought over the counter NSAIDs or aminosalicylic acid, respectively.49
Non-differential misclassification on exposure would, however, tend to bias the results towards the null. Secondly, by starting the study on the date that rofecoxib became available (1 April 2000), we included only incident users of rofecoxib but incident and prevalent users of celecoxib. We considered whether the results favouring celecoxib may have been the result of attrition and adherencebiases.50
We carried out a sensitivity analysis in which we included only new users of celecoxib (and excluded those with a prescription before 1 April 2000). Time to all cause death or recurrent congestive heart failure was similar to that reported in the main analysis (hazard ratio 1.27, 95% confidence interval 1.07 to 1.52 versus 1.27, 1.09 to 1.49).
What is already known on this topic
Non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of congestive heart failure
Little is known about the safety of cyclo-oxygenase-2 inhibitors in patients with congestive heart failure
What this study adds
Celecoxib seems to be a safer alternative to rofecoxib and NSAIDs in elderly patients with congestive heart failure
Class differences seem to exist between NSAIDs and cyclo-oxygenase-2 inhibitors and between cyclo-oxygenase-2 inhibitors
NSAIDs are known to be associated with congestive heart failure, but such information is scarce for cyclo-oxygenase-2 inhibitors. No head to head comparisons in randomised trials are available to determine the relative risks between NSAIDs and cyclo-oxygenase-2 inhibitors. We used an observational design and compared a cohort of patients with congestive heart failure who used NSAIDs or cyclo-oxygenase-2 inhibitors, and we found that celecoxib was associated with a lower risk of death and recurrent congestive heart failure than were NSAIDs and rofecoxib. All our patients received either NSAIDs or a cyclo-oxygenase-2 inhibitor and the reference group received celecoxib. Since we had no unexposed group, we were unable to estimate whether, and by how much, celecoxib increases the risk of recurrent congestive heart failure and death compared with non-users of NSAIDs and cyclo-oxygenase-2 inhibitors. We conclude that important class differences seem to exist between NSAIDs and cyclo-oxygenase-2 inhibitors and among cyclo-oxygenase-2 inhibitors themselves. Celecoxib seems to be a safer alternative to rofecoxib and NSAIDs in elderly patients with congestive heart failure.