(CNN) Over the past decade, doctors have suspected that celecoxib, a pain-relieving nonsteroidal anti-inflammatory drug, or NSAID, increases heart risks more than older NSAIDs. But a new study, published Sunday in the New England Journal of Medicine, lays those fears to rest.

A three-way comparison of prescription doses of Celebrex (celecoxib), Naprosyn (naproxen) and Motrin (ibuprofen) showed little difference in arthritis patients' risk of heart failure, heart attack or stroke, with Celebrex proving marginally safer than the others.

"In 2013, there were 100 million prescriptions written for NSAIDs, so these results affect almost everybody," said Dr. Steve Nissen, lead investigator of the new study and chairman of the department of cardiovascular medicine at the Cleveland Clinic. He presented his findings at the American Heart Association's annual scientific meeting in New Orleans Sunday.

The study began 10 years ago and involved nearly 1,000 medical centers around the world. The researchers equally divided more than 24,000 osteoarthritis or rheumatoid arthritis patients into three groups. Each group was assigned prescription doses of either celecoxib, naproxen or ibuprofen.

More than half (64%) of the participants were women. The average age of participants was 64. All had been diagnosed with heart disease or had an increased risk for developing cardiovascular problems along with their arthritis condition.

Though the main purpose of the study was to see whether celecoxib raised the risk of heart problems in this group of patients, Nissen and his colleagues also assessed whether all or any of the three drugs were associated with serious gastrointestinal upset, kidney complications or death.

"Until you do the studies, you can make bad judgments about what is safe and effective," Nissen said, adding that the new study "didn't show what we thought."

Heart risks

Celebrex did not prove more risky than the two older drugs. In fact, heart attack, stroke or cardiovascular death occurred in 2.3% of the patients taking celecoxib, 2.5% of those taking naproxen and 2.7% of those taking ibuprofen.

All the participants also received Nexium (esomeprazole), a drug that reduces stomach acid, for "gastric protection." The risk of ulcers, chronic bleeding and other gastrointestinal problems are known complications of older-generation NSAIDs. As might be expected, the new study showed that the rate of ulcers or gastrointestinal bleeding was 54% higher for ibuprofen and 41% higher for naproxen, compared with celecoxib.

Another possible complication is worse kidney function. The study results indicated that participants in the ibuprofen group had a 64% higher risk of kidney problems compared with those taking celecoxib. Nissen pointed out that, until now, this had been unknown because it had never been studied.

The overall likelihood of a patient experiencing any negative side effect, whether cardiovascular, gastric or renal (kidney), was 28% higher for patients taking ibuprofen and 15% higher for patients taking naproxen compared to patients taking celecoxib, said Nissen.

Dr. Milton Pressler, a cardiologist and vice president and head of clinical affairs for Pfizer Essential Health -- the company that makes Celebrex -- emphasized that this study examined daily prescription doses of all three drugs. Because the researchers did not investigate occasional use at lower doses, the study results do not indicate over-the-counter versions of these drugs may be unsafe.

"This is about chronic use and prescription strength," said Pressler, who headed up the Pfizer team working on this study.

"Occasional, short-term use of the over-the-counter naproxen sodium dose as found in Aleve was not studied," said Andre Schmidt, vice president of U.S. Medical Affairs, Consumer Health, Bayer, maker of naproxen. He added that Aleve is safe and risk of a serious gastrointestinal side effect is rare when taken as directed.

Motrin maker Johnson & Johnson's McNeil Consumer Healthcare Division also noted that the study evaluated ibuprofen at doses far exceeding the maximum specified on the over-the-counter Motrin label.

Although the labels of over-the-counter drugs do specify proper use, consumers do not always follow the directions.

"We have to warn people because of dose creep," Nissen said. The term refers to the fact that over time, some people will gradually increase the number of over-the-counter pills they take. In some cases, they end up taking prescription-strength doses. Which is why he said transparency of his findings is so important.

The authors pointed out two weaknesses in their work. First, the study lacked a comparison to a placebo. However, it is not considered ethical to include a placebo group in a study of patients in pain, Nissen explained.

Another limitation of the study: about two-thirds of participants did not complete the trial.

"That really raised a red flag for me," said Dr. Suzanne Steinbaum, director of women's heart health at Northwell Lenox Hill Hospital in New York, who was not involved in the study. "That's a very significant dropout rate."

According to Pressler, patients in pain often change their mind midway through a study since "pain comes and goes." He thinks it's "fair to say" Pfizer, the Cleveland Clinic and the FDA expected this issue and specifically designed the study to begin with many participants and to continue following those who decided to withdraw.

"We think we did well compared to other pain studies in keeping patients in the study and being evaluated," said Pressler.

Extensive research

NSAIDs relieve physical aches by blocking the production of prostaglandins, chemicals in the body that cause pain and inflammation. Ibuprofen received approval from the FDA in 1974 and naproxen in 1976. Though effective pain-relievers, these early NSAIDs increased the risk of gastrointestinal complications.

Celecoxib and rofecoxib were introduced in 1999 and specifically intended to reduce those risks.

Vioxx (rofecoxib) proved an immediate success. The drug, which was commonly prescribed to arthritis patients, reached $2.5 billion in sales across more than 80 countries by 2003. But when a three-year cancer trial showed that patients taking Vioxx experienced a heightened risk of heart attack and stroke after 18 months of high-dosage use, maker Merck withdrew Vioxx from the market.

"Vioxx was one of the biggest safety events in drug history," Nissen said.

An unrelated 2004 study raised questions about the potential risks of prescription-strength celecoxib. In 2005, the FDA responded to this news by advising Pfizer that Celebrex could stay on the market if the company continued to study potential heart risks associated with the drug.

A year later, Nissen and Pfizer began the specially designed study of arthritic patients at high cardiovascular risk to comply with the FDA advisory.

Importantly, Celebrex went off-patent in the United States and Europe two years ago, so the generic can now be produced by competitors. However, Pfizer retains the patent in Japan until 2016.

"This was never about the patent -- this was about patient safety," said Pressler, who explained Pfizer carries out studies to validate the safety of its products all the time. Asked if Pfizer is hoping to create an over-the-counter version of Celebrex, which is a prescription drug, he said it's under consideration and will ultimately be for the FDA to decide.

Nissen said the new results prove that previous assumptions about Celebrex based on Vioxx are simply incorrect.

"I've been telling my patients for 10 years that if they have arthritis and have to take a drug, naproxen is safest," said Nissen, who presented the research Sunday at the American Heart Association conference in New Orleans. "I've been wrong. I drank the Kool-Aid."

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Steinbaum agreed. "As a cardiologist and as a patient," Celebrex can be considered a safe option for pain relief -- "and it might be better in terms of side effects."

However, Nissen and his co-authors concluded that their results do not tell us about the effects of the more than two dozen other NSAIDs marketed in the United States.

"At the end of the day, NSAIDs are not great for us. There are side effects to every medication," Steinbaum said. "What I tell people is, the lowest dose you can get away with, the better it is."