More than a decade after initial concerns about the safety of COX-2 inhibitors, the PRECISION trial has shown celecoxib is non-inferior to either ibuprofen or naproxen in respect to cardiovascular risk.
The study published in the New England Journal of Medicine found 200mg/day of celecoxib for arthritic pain did not increase the risk of major adverse events including cardiovascular deaths, myocardial infarction or stroke.
However the scale of the study – 24,000 patients across 926 centers in 13 countries – has not protected it from some criticism.
Professor Graeme Jones, head of the musculoskeletal research group at the Menzies Institute for Medical Research, said the findings were reassuring and were probably the best data that would be available yet there were several limitations.
“With an event rate of about 1% per annum, it was a relatively low risk group despite inclusion criteria for established cardiovascular disease or increased risk,” Professor Jones told the limbic.
He said the fact that 46% of participants were using aspirin was also a concern.
“We’re not sure what the aspirin is doing but we presume it is cardioprotective. The data is not clear how that affects the analysis.”
Additionally, he said the dose escalation of ibuprofen to a mean daily dose of 2045mg and naproxen to 852mg increased the risk of cardiovascular events in those groups.
“If all drugs increase cardiovascular risk at higher doses and the dose is only escalated in two of the three groups, then the findings are likely to favour celecoxib,” Professor Jones said.
He said the findings were however broadly consistent with earlier studies and were unlikely to change current practice.
A perspective piece on the PRECISION trial published in Circulation echoed his comments about the low number of events, pharmaco-equivalence and aspirin.
“…it is unknown who took aspirin throughout the study and whether, if they did, cardiovascular events might have ensued in the ibuprofen and naproxen groups due to an interaction undermining the anti-platelet effects of the drug,” the author Dr Garret FitzGerald said.
Dr FitzGerald, from the Institute for Translational Medicine and Therapeutics at the
University of Pennsylvania, also highlighted the high rate of study participants who stopped taking their drug (69%) and loss to follow-up (27%).