Celecoxib, a cyclooxytenase-2 (COX-2) inhibitor, is comparable to naproxen and ibuprofen in cardiovascular safety for patients with arthritis at high risk for cardiovascular disease (CVD), according to data released at the 2016 American Heart Association (AHA) Scientific Sessions1 and published simultaneously online in the New England Journal of Medicine.2
Steven Nissen, MD, chairman of the Robert and Suzanne Tomsich Department of Cardiovascular Medicine at Cleveland Clinic’s Sydell and Arnold Miller Family Heart & Vascular Institute, presented the findings at the AHA. “These findings challenge the widely-held view that naproxen provides superior cardiovascular safety,” he said.
Results of the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen; ClinicalTrials.gov identifier: NCT00346216) trial found that celecoxib achieved noninferiority for the Antiplatelet Trialists Collaboration (APTC) composite outcome of CV death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke for the on-treatment as well as the intention-to-treat (ITT) populations.
“Numerically fewer APTC events occurred with celecoxib than naproxen, and fewer APTC events occurred with celecoxib than ibuprofen,” Dr Nissen summarized, adding that celecoxib met all 4 noninferiority criteria for both NSAIDs (P <.001).
A total of 24,081 patients were randomly assigned to the celecoxib group, the naproxen group, or the ibuprofen group for mean treatment duration of 20.3 ± 16.0 months and a mean follow-up period of 34.1 ± 13.4 months.
During the trial, 68.8% of the patients stopped taking the study agent, and 27.4% of the patients discontinued at follow-up. “Adherence and retention were lower than other CV outcome trials, although similar to other pain studies,” Dr Nissen commented.
In the intention-to-treat analyses, a primary outcome event occurred in 188 patients (2.3%) in the celecoxib group, 201 patients (2.5%) in the naproxen group, and 218 (2.7%) patients in the ibuprofen group; (hazard ratio [HR] for celecoxib vs naproxen: 0.93; 95% confidence interval [CI], 0.76-1.13; HR for celecoxib vs ibuprofen: 0.85; 95% CI, 0.70-1.04; P <.001 for noninferiority in both comparisons).
In the on-treatment analysis, a primary outcome event occurred in 134 patients (1.7%) in the celecoxib group, 144 patients (1.7%) in the naproxen group (1.8%), and 155 patients (1.9%) in the ibuprofen group; (HR for celecoxib vs naproxen: 0.90; 95% CI, 0.71-1.15; HR for celecoxib vs. ibuprofen: 0.81; 95% CI, 0.65-1.02; P <.001 for noninferiority in both comparisons).
Comparitive safety analysis showed that the risk of gastrointestinal events was significantly lower with celecoxib than with naproxen (P =.01) or ibuprofen (P =.002); the risk of renal events was significantly lower with celecoxib than with ibuprofen (P =.004) but was not significantly lower with celecoxib than with naproxen (P =.19).
Dr Nissen cautioned that “between-drug differences should be viewed as hypothesis-generating, rather than conclusive.” Moreover, “the results reflect the relative safety of these3 drugs and not the more-than 20 other currently-marketed NSAIDs.”
He added, “These findings will require careful review by global health authorities to determine what changes in labeling or regulatory status of these drugs are warranted.”
Disclosures: This study was funded by Pfizer. A full list of disclosures is available at NEJM.org.
- Nissen, SE. Cardiovascular outcomes with celecoxib vs ibuprofen or naproxen: the PRECISION trial. LBCT.01: Big Trials for Big Ideas. November 14, 2016. Presented at: the 2016 American Heart Association Scientific Sessions. November 12-16, 2016; New Orleans, LA.
- Nissen SE, Yeomans ND, Solomon DH, et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med 2016. doi:10.1056/NeJMoa1611593 [Epub ahead of print].