1 March 2006
Celecoxib increases risk of heart attack, new study finds
A study published in the March issue of the Journal of the Royal Society of Medicine, has found celecoxib increases the risk of a heart attack by over two-fold.
Celecoxib is the most commonly used COX-2 inhibitor drug in the treatment of arthritis and acute pain. It is manufactured by Pfizer and marketed under the brand name Celebrex.
"Our evidence shows an increased risk of heart attack in patients taking celecoxib," said Professor Richard Beasley of New Zealand’s Medical Research Institute.
"Drug regulatory authorities need to urgently re-examine the assessment of the drug in light of these findings."
Cyclooxygenase-2 (COX-2) inhibitor drugs are popular analgesics as they have fewer gastrointestinal side effects than traditional NSAIDs like ibuprofen and diclofenac.
However, the extent to which use of COX-2 inhibitors increase the risk of cardiovascular events has been the subject of considerable debate in the last two years.
Rofecoxib, also a COX-2 inhibitor drug, was manufactured by drug company Merck under the name Vioxx but voluntarily withdrawn worldwide following evidence linking it to an increase in the risk of heart attacks and stroke.
Professor Beasley undertook a systematic review and meta-analysis of randomized double-blind clinical trials of celecoxib of at least six weeks' duration and which presented data on serious cardiovascular events.
Specifically, the researchers examined whether the increased risk of cardiovascular events with rofecoxib was also present with celecoxib and thus represented a class effect of COX-2 inhibitors.
Four placebo-controlled trials with 4422 patients were included in the primary meta-analysis comparing celecoxib with placebo. The findings show the use of celecoxib was associated with a 2.26-fold increased risk of myocardial infarction when compared to a placebo.
The second meta-analysis included a total of six studies of 12,780 patients and demonstrated a 1.88-fold increased risk of myocardial infarction when celecoxib was compared with all comparator treatment groups including ibuprofen, paracetomol and diclofenac.
"These findings are critical as the risk is similar in magnitude to the 2.24-fold increased risk of heart attack with Vioxx as reported in a comparable meta-analysis," said Professor Beasley.
"Given the popularity of celecoxib in the treatment of arthritis, drug regulators must undertake an up-to-date risk assessment based on the findings presented here."
Currently, the European Medicines Agency’s advice is COX-2 inhibitors should not be used in patients with heart disease or stroke and doctors should use the lowest effective dose of the COX-2 medicine for the shortest possible duration of treatment.
"It will be interesting to see if the drug regulators tighten restrictions and whether celecoxib is now withdrawn as occurred with Vioxx," Professor Beasley said.
JRSM Editor, Kamran Abbasi, said controversy had raged for almost two years about the safety of this class of drug.
"The early warnings on Vioxx went unheeded. We can only hope that clinicians and regulatory authorities around the world will not make the same mistake twice. This is another lesson that wonder drugs often come with a sting in the tail," Dr Abbasi said.
In contrast to the increased risk of myocardial infarction, this study did not identify a corresponding increased risk of cerebrovascular events.
'Risk of cardiovascular events and celecoxib: a systematic review and meta-analysis' by B Caldwell, S Aldington, M Weatherall, P Shirtcliffe and R Beasley is published in the March issue (Vol. 99) of the Journal of the Royal Society of Medicine.
JRSM is the flagship journal of the Royal Society of Medicine. It has been published continuously since 1809. Its Editor is Dr Kamran Abbasi.