Heart Risks of Celebrex ‘Dispelled,’ Drugmaker Says

Pfizer sponsors comparison with ibuprofen and naproxen

Results from the landmark PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen Or Naproxen) trial demonstrated similar rates of cardiovascular (CV) risk in patients treated with prescription doses of celecoxib, ibuprofen, and naproxen who had a clinical diagnosis of osteoarthritis (OA) or rheumatoid arthritis (RA), were at high risk for CV disease, and required daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) to control symptoms of arthritis.

In addition, patients treated with celecoxib experienced significantly fewer gastrointestinal (GI) events compared with those receiving prescription doses of ibuprofen or naproxen. According to Pfizer, the trial’s sponsor, the PRECISION study helps to refute the assumption held by many physicians that naproxen treatment results in better CV outcomes compared with other NSAIDs, including celecoxib. Given the trial’s design––prescription doses and chronic use in patients with CV risk factors––no inferences are possible regarding the safety of intermittent use of low-dose, over-the-counter NSAIDs.

The results were published in the New England Journal of Medicine.

The PRECISION study was a prospective, long-term noninferiority trial designed to assess the CV safety of celecoxib (Celebrex, Pfizer) compared with that of prescription-strength doses of ibuprofen and naproxen in 24,081 patients with chronic pain from OA or RA. Although the trial was funded by Pfizer, it was directed independently by the Cleveland Clinic and governed by an executive committee composed of cardiology, gastroenterology, and rheumatology specialists.

The study’s primary objective was to assess the effects of celecoxib (100 mg or 200 mg twice daily) compared with those of prescription-strength doses of ibuprofen (600 mg or 800 mg three times daily) or naproxen (375 mg or 500 mg twice daily) on the first occurrence of CV death, nonfatal myocardial infarction, or nonfatal stroke in subjects with OA or RA who had established CV disease or risk factors for CV disease. All of the subjects were provided with esomeprazole, a proton pump inhibitor (PPI), to be taken once daily as a gastroprotective agent. The subjects also had the option of continuing low-dose aspirin for additional cardioprotective effects regardless of their CV risk.

The final trial results provided evidence that the CV risk with approved doses of celecoxib is not greater than that of prescription doses of ibuprofen and naproxen. The study showed that subjects with chronic arthritic conditions and CV risk factors taking celecoxib experienced numerically fewer CV events compared with subjects receiving prescription-strength doses of ibuprofen and naproxen. Specifically, the primary endpoint occurred in 2.3% of patients receiving celecoxib compared with 2.5% of those receiving naproxen and 2.7% of those receiving ibuprofen.

Regarding secondary analyses, significantly fewer GI events occurred among patients treated with celecoxib compared with those receiving prescription doses of ibuprofen or naproxen. Specifically, serious GI events occurred in 1.1% of the celecoxib group compared with 1.5% and 1.6% of the naproxen and ibuprofen groups, respectively. The GI safety findings were observed despite providing all patients enrolled in the study with a PPI to reduce stomach acid. In addition, a secondary endpoint involving renal events occurred less often in patients treated with celecoxib compared with those given prescription doses of ibuprofen.

Source: Pfizer; November 13, 2016.