Pfizer announced that results of the PRECISION study demonstrated similar rates of cardiovascular risk in patients treated with prescription doses of the company's Celebrex (celecoxib) versus ibuprofen and naproxen in patients with osteoarthritis or rheumatoid arthritis. The trial included patients who were at high risk for cardiovascular disease and required daily treatment with non-steroidal anti-inflammatory drugs (NSAIDs).
Ian Read, Pfizer's chief executive, remarked "questions about the cardiovascular safety of prescription NSAIDs have persisted since the withdrawal of Vioxx (rofecoxib) from the market in 2004." Read added that the PRECISION study "dispels the long held perception of excess cardiovascular risk associated with long-term use of Celebrex."
The trial included 24 081 patients and was designed to assess the cardiovascular safety of Celebrex versus prescription strength doses of ibuprofen and naproxen in patients with chronic pain from osteoarthritis or rheumatoid arthritis. The study's main goal was to assess the effects of Celebrex compared to the two other drugs on the first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. Meanwhile, pre-specified secondary objectives included assessments of additional cardiovascular endpoints, significant gastrointestinal events, renal events and arthritis pain improvement.
Results, which were published in the NEJM and presented at the American Heart Association (AHA) annual meeting, demonstrated that the primary endpoint occurred in 2.3 percent of patients receiving Celebrex, compared to 2.5 percent for those on naproxen and 2.7 percent for patients taking ibuprofen. "We can conclude most definitively here that Celebrex does not increase the risk of major cardiovascular events in comparison to the older drugs. It is non-inferior," remarked lead investigator Steven Nissen.
Results also showed that patients treated with Celebrex experienced significantly fewer gastrointestinal events as compared with those receiving naproxen or ibuprofen, with rates of 1.1 percent, 1.5 percent and 1.6 percent, respectively. Further, data indicated that the risk of renal events was significantly lower with Celebrex than with ibuprofen, but not when compared to naproxen.
Commenting on the study, Elliott M. Antman, a professor of medicine at Harvard Medical School and a past president of the AHA, noted that only a minority of the patients actually had documented heart disease and it is those patients who are most worrisome, while many dropped out, making it hard to interpret the data. Over the course of the trial, 68.8 percent of the patients stopped taking the drug they were assigned to, and 27.4 percent of the subjects discontinued follow-up. "They asked an important question, but the trial was hard to complete," Antman said, adding the weaknesses of the study made him unable to be confident of its conclusions.
Last year, an FDA issued a safety communication strengthening an existing label warning that non-aspirin NSAIDs increase the chance of a heart attack or stroke. At the time, the agency said there is not enough data yet to conclude whether the risk of any particular NSAID is definitely higher or lower than another. Milton Pressler, a cardiologist in charge of clinical affairs for Pfizer Essential Health, said the company is now "sifting through more than three million pages of data and putting together a comprehensive report" to send to the FDA. Annual sales of Celebrex were about $3 billion in 2014, although the drug is now available generically.
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