There are fewer Antiplatelet Trialists Collaboration (APTC) events with celecoxib than with naproxen or ibuprofen, and higher rates of gastrointestinal adverse events with naproxen or ibuprofen than with celecoxib, according to results of a post-marketing cardiovascular safety analysis of celecoxib, presented at the 2016 Annual Meeting of the American Heart Association (AHA).
When the cyclooxygenase type 2 (COX-2) selective inhibitor rofecoxib was withdrawn from the market in 2004 because of increased risks of heart attack and stroke associated with its long-term, high-dosage use, the US Food and Drug Administration required a safety trial comparing the only remaining COX-2 selective inhibitor, celecoxib, with traditional non-selective NSAIDs.
Celecoxib met all 4 noninferiority criteria (P < 0.001), noted lead investigator, Steven E. Nissen, MD, Cleveland Clinic, Cleveland, Ohio, speaking here at a press briefing on November 13. “These findings challenge the widely held view that naproxen provides superior cardiovascular safety,” he added.
The aim of the Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen Or Naproxen (PRECISION) trial was to evaluate effects of celecoxib (100 to 200 mg twice daily) and ibuprofen (600 to 800 mg three times daily) compared with naproxen (375 to 500 mg twice daily) on the first occurrence of an APTC composite cardiovascular endpoint (cardiovascular death, nonfatal myocardial infarction or nonfatal stroke) in 24,081 patients (mean age 63 years; 74.3% white; 64.1% female) in 13 countries all of whom either had osteoarthritis or rheumatoid arthritis with or at high risk for concomitant cardiovascular disease.
For the APTC endpoint, celecoxib was noninferior to ibuprofen and naproxen in both intention-to-treat and in on-treatment analyses.
Superiority analyses, which Dr. Nissen cautioned could only be considered as hypothesis-generating, demonstrated a borderline benefit (15%, P = .06) for celecoxib versus ibuprofen for time to major adverse cardiovascular events, and for celecoxib versus naproxen for time from randomisation to all-cause mortality (25%, P = .052).
Intention-to-treat benefits for celecoxib in time to major gastrointestinal event were significant compared with ibuprofen (54%, P = .002) and to naproxen (41%, P = .01). Also, an analysis of time from randomisation to serious renal event demonstrated a highly significant benefit for celecoxib versus ibuprofen (64%, P = .004).
Drug discontinuation rates were similar for all agents (approximately 69%).
Aspirin (75 to 100 mg daily) was allowed according to local guidelines, and was administered at baseline to 51.1% of patients. The primary diagnosis was rheumatoid arthritis in 10.1% of patients and osteoarthritis in 89.9%. Patients were provided with daily esomeprazole for gastrointestinal protection.
Dr. Nissen cautioned that “between-drug differences should be viewed as hypothesis-generating, rather than conclusive, given a multiplicity of issues and the challenges of adherence and retention in the trial.”
NSAIDS and celecoxib inhibit cyclooxygenase, reducing pain and inflammation through inhibition of prostaglandins in patients with osteoarthritis and rheumatoid arthritis.
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