Selective cyclooxygenase inhibitors may retard the progression of cancer, but they have enhanced thrombotic potential.
Dr David Kerr and colleagues from England reported on cardiovascular adverse events in patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer.
All serious adverse events that were cardiovascular thrombotic events were reviewed in 2434 patients with stage II or III colorectal cancer.
The team performed a randomized, placebo-controlled trial of rofecoxib, 25 mg daily, started after potentially curative tumor resection and chemotherapy or radiotherapy as indicated.
The trial was terminated prematurely owing to worldwide withdrawal of rofecoxib.
|The overall unadjusted relative risk was 1.50|
|New England Journal of Medicine|
To examine possible persistent risks, the research team examined cardiovascular thrombotic events reported up to 24 months after the trial was closed.
The median duration of active treatment was 7 months.
The researchers matched 1167 patients receiving rofecoxib with 1160 patients receiving placebo.
The median follow-up period was 33 months.
Of the 23 confirmed cardiovascular thrombotic events, 16 occurred in the rofecoxib group during or within 14 days after the treatment period.
The research team found that the estimated relative risk was 2.66.
Analysis of the Antiplatelet Trialists' Collaboration end point gave an unadjusted relative risk of 1.60.
The endpoints included combined incidence of death from cardiovascular, hemorrhagic, and unknown causes.
Nonfatal myocardial infarction, nonfatal ischemic, and hemorrhagic stroke were also assessed.
The team identified 14 more cardiovascular thrombotic events, 6 in the rofecoxib group, within the 2 years after trial closure.
The overall unadjusted relative risk was 1.50.
The team noted that 4 patients in the rofecoxib group, and 2 in the placebo group died from thrombotic causes during or within 14 days after the treatment period, and during the follow-up period.
The team reported that 1 patient in the rofecoxib group, and 5 patients in the placebo group died from cardiovascular causes.
Dr Kerr's team comments, "Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular events among patients with a median study treatment of 7.4 months' duration."