Selective inhibition of cyclooxygenase-2 may be associated with an increased risk of thrombotic events, but only limited long-term data have been available for analysis.
Dr Brasalier and colleagues designed a long-term, multicenter, randomized, placebo-controlled, double-blind trial.
The researchers aimed to determine the effect of 3 years of treatment with rofecoxib on the risk of recurrent neoplastic polyps of the large bowel in patients with a history of colorectal adenomas.
The research team also reported on the cardiovascular outcomes associated with the use of the selective cyclooxygenase-2 inhibitor rofecoxib.
The team randomized a total of 2,586 patients with a history of colorectal adenomas of which 1,287 received 25 mg of rofecoxib daily, and 1,299 received placebo.
All investigator-reported serious adverse events that represented potential thrombotic cardiovascular events were adjudicated in a blinded fashion by an external committee.
The investigators noted that a total of 46 patients in the rofecoxib group had a confirmed thrombotic event during 3,059 patient-years of follow-up (1.5 events per 100 patient-years).
The previous result was compared by the team with 26 patients in the placebo group who had confirmed thrombotic event during 3,327 patient-years of follow-up (0.8 event per 100 patient-years).
The corresponding relative risk was 1.9.
| The increased relative risk became apparent after 18 months of treatment|
|New England Journal of Medicine|
The researchers observed that the increased relative risk became apparent after 18 months of treatment; during the first 18 months, the event rates were similar in the two groups.
The results reported by the investigators primarily reflect a greater number of myocardial infarctions and ischemic cerebrovascular events in the rofecoxib group.
At approximately 5 months, there was earlier separation between groups in the incidence of nonadjudicated investigator-reported congestive heart failure, pulmonary edema, or cardiac failure.
The research team, however, showed that overall and cardiovascular mortality was similar in the two groups.
Dr Bresalier concludes, “Among patients with a history of colorectal adenomas, the use of rofecoxib was associated with an increased cardiovascular risk.”