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PRECISION: Celecoxib Not Inferior to Ibuprofen, Naproxen in Cardiovascular Safety
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WASHINGTON — Compared with ibuprofen and naproxen, celecoxib demonstrated non-inferiority with regard to cardiovascular safety, according to data presented at the American College of Rheumatology Annual Meeting.
“With the withdrawal of rofecoxib for adverse cardiovascular events, there were questions raised about the safety of all NSAIDs, including the remaining selective COX-2 inhibitor celecoxib,” Daniel H. Solomon, MD, MPH, from the Division of Rheumatology at Brigham and Women’s Hospital and Harvard Medical School, said during his presentation, here. “However, there have been few direct comparison of NSAID safety and no randomized trials prospectively designed for [cardiovascular] CV safety.”
As part of the PRECISION trial, Solomon and colleagues performed a double-blind, randomized control non-inferiority trial of 24,081 patients with osteoarthritis (OA) or rheumatoid arthritis (RA) and a known history of cardiovascular events, such as stroke, myocardial infarction or coronary re-vascularization. The patient criteria also included daily NSAID therapy, no cardiovascular events within the last 90 days and no contraindications to the use of celecoxib. Patients received either 100 mg to 200 mg of celecoxib, 600 mg to 800 mg of ibuprofen or 375 mg to 500 mg of naproxen. All patients were provided aspirin and 20 mg to 40 mg of esomeprazole, if needed.
Primary cardiovascular outcome was cardiovascular death, non-fatal myocardial infarction and non-fatal stroke with at least an 18-month follow-up. The trial continued for 10 years until enough data could be accumulated. The 24,081 patients came from 13 countries and 923 sites, with 80% of patients from the United States. Overall, 90% of patients had OA, with a mean age of 63.5 years and 63.1% of whom were female. Additionally, 10% of patients had RA with a mean age of 60.7 years and 73.2% of whom were female. After 6 months of follow-up, researchers reported 80% of patients adhered to treatment.
According to Solomon, the numbers of events were numerically lower in the celecoxib group in all cardiovascular outcomes. In the OA group, there was a 16% reduction in major adverse cardiac events in celecoxib users compared with the ibuprofen users. For the RA patients, all three treatment arms were “almost superimposable,” he said, suggesting a similar cardiac event rate for each treatment.
For gastrointestinal events in the patients with OA, Solomon said celecoxib showed a 32% reduction in risk compared with ibuprofen and a 27% reduction compared to naproxen. There was not significant reduction in gastrointestinal events for patients with RA. In the OA group, there was a 42% lower event rate in celecoxib users vs. ibuprofen users and event curves for rheumatoid arthritis were similar, he said.
In all-cause mortality, patients with osteoarthritis had similar cumulative event curves for all three treatment groups. For RA, celecoxib users had 50% about fewer deaths, Solomon said. There was also an increase in renal events in the comparison of ibuprofen with celecoxib in patients with OA.
“I think we have learned these NSAIDs do have a unique safety profile,” M. Elaine Husni, MD, from the Division of Rheumatology at the Cleveland Clinic and a study co-author, said in a press conference held here. “They are different and they can be different in different groups when we followed them long term. Overall, the message is that celecoxib is not inferior to ibuprofen or naproxen.” – by Will Offit
Reference:
Husni ME, et al. Abstract #1L. Presented at: American College of Rheumatology Annual Meeting; Nov. 11-16, 2016; Washington.
Disclosures: Husni reports relationships with Eli Lilly, Novartis, AbbVie, Celgene, Bristol Myers Squibb, Amgen, Janssen, UCB Pharma and Pfizer. Solomon reports a relationship with Pfizer. Please see the abstract for a list of all other authors’ relevant financial disclosures.
Perspective
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Calvin R. Brown Jr., MD
The long-awaited PRECISION Trial of cardiovascular safety of celecoxib was finally released and presented at the American College of Rheumatology Annual Meeting and almost simultaneously at the American College of Cardiology Annual Meeting in New Orleans. It has taken 10 years, after the withdrawal of Vioxx, to get this answer. The primary endpoint was a non-inferiority one for celecoxib compared to either naproxen or ibuprofen for cardiovascular events. The lowest event rates were with celecoxib, but not statistically lower than ibuprofen or naproxen, but it was clearly non-inferior. Therefore, we now know risks that were seen with rofecoxib do not seem to be shared by celecoxib. There were some safety differences favoring celecoxib in secondary endpoints.
The take-home for rheumatologists is we can certainly be comfortable giving our patients with increased cardiovascular risk celecoxib when they require anti-inflammatory agents to function on a daily basis. Of course, our cardiology colleagues say "the lowest dose for the shortest time you can,” but we in rheumatology don’t always have that luxury.
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