A 10-year investigation, results of which were published in November 2016, gives a nod to use of celecoxib in patients who take the drug regularly for arthritis, even if they are at high risk for cardiovascular disease. The study authors concluded that moderate, regular doses of celecoxib were no riskier than similar doses of ibuprofen and naproxen in a randomized controlled trial of 24,000 patients at risk for heart disease.1

Not only did the study demonstrate that celecoxib poses no greater risk for heart attack than 2 other commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), it indicated that celecoxib has significantly better effects in at least 2 other disease processes. Of the 3 drugs studied, celecoxib had a lower risk than ibuprofen for worsening kidney function. Furthermore, patients taking either ibuprofen or naproxen were significantly more likely to be hospitalized for hypertension.

And, despite the assumption by the authors that naproxen was the safest of the 3 NSAIDs, there were 25% more total deaths with naproxen than celecoxib: 163 with naproxen compared with 132 with celecoxib.

The study published online in November 2016 in the New England Journal of Medicine was dubbed the Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION) trial.1

Some questions remain. The study did not include a placebo group, for example, so it was not able to demonstrate whether any increased risk might exist with all 3 drugs.

A physician who was not involved in the study, Elliott M. Antman, MD, professor of medicine at Harvard Medical School and a past president of the American Heart Association, noted in an article in the New York Times that only a minority of the patients had documented heart disease, and that it is those patients who are most worrisome. Many such patients dropped out of the study, he noted, making it hard to interpret the data.2

"They asked an important question, but the trial was hard to complete," Antman told the New York Times. The weaknesses of the study made him unable to be confident of its conclusions, he said. However, he added, "this is the best we will get" and "we will probably never see another study like this."2

Antman told the newspaper that he would continue to advise that any of these drugs be taken only by the lowest-risk patients in the lowest effective dose for the shortest possible time.

Pfizer paid for the study. However, members of the study's executive committee, all of whom were academic researchers, agreed not to accept payments from any maker of NSAIDs for the duration of the trial.

Even the authors expressed some surprise at their results. Twelve years ago, rofecoxib was pulled from the market because of evidence of increased cardiovascular risk. Both rofecoxib and celecoxib are cyclooxygenase-2 (COX-2) inhibitors. Although celecoxib remained on the market and in use, it existed under a shadow while researchers conducted the PRECISION trial at the request of the FDA.

Steven E. Nissen, MD, the lead author of the PRECISION study, had been among the researchers who discovered the risks of rofecoxib in 2004, calling it "one of the most important safety events ... in recent medical history."3

"Celebrex is a drug that has a very similar method of action to [rofecoxib] and so the FDA was worried that Celebrex might share the same risk," said Nissen, chair of the department of cardiovascular medicine at Cleveland Clinic's Sydell and Arnold Miller Family Heart and Vascular Institute. There was even some evidence already pointing to it, he added.2

An estimated 2 million people in the United States take Celebrex or generic celecoxib, according to Milton Pressler, MD, a cardiologist in charge of clinical affairs for Pfizer Essential Health. The patent on the drug expired during the trial, so it is also now made and sold in generic form.2

Pressler told the New York Times that Pfizer is now "sifting through more than three million pages of data and putting together a comprehensive report" to send to the FDA. Then, he said, it will be up to the agency to decide what changes, if any, should be made to the drug's label, which currently warns against heart and gastrointestinal effects.

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