Anti-inflammatory medications and the risk for cardiovascular disease: A new study, a new perspective

Robert H. Shmerling, MD

Senior Faculty Editor, Harvard Health Publishing

Follow me on Twitter  @RobShmerling

News last week about celecoxib shows how challenging it can be to understand the risks and benefits of newly developed drugs. This is particularly true when the findings of one study contradict those of past studies. And that’s exactly what has happened with celecoxib.

Anti-inflammatory medications: pros and cons

The FDA approved celecoxib (Celebrex) in 1999. This anti-inflammatory medication can be a highly effective treatment for arthritis and other painful conditions. It was developed with the hope that it would be at least as effective as other anti-inflammatory medications (such as ibuprofen or naproxen) but cause less stomach irritation. Developing a safer anti-inflammatory medication is a worthy goal, since stomach irritation can not only cause annoying pain or nausea, but it can also lead to ulcers, bleeding, or perforation. These medications can also increase blood pressure and cause kidney problems.

Celecoxib is known as a COX-2 inhibitor — that’s because it targets an enzyme (COX-2) involved in inflammation. Ibuprofen and naproxen (and many other anti-inflammatories) target COX-1 and COX-2. They’re called “non-selective” anti-inflammatory drugs. Because of where these enzymes are found in the body, the COX-2 selective medications seemed capable of dampening down inflammation while going easier on the stomach.

And that was true. Celecoxib — and other COX-2 inhibitors, such as rofecoxib (Vioxx) — did cause less stomach trouble. But soon after its approval, studies suggested other concerns: an increased risk of heart attack and stroke. Rofecoxib was removed from the market in 2004. And while the FDA allowed celecoxib to remain on the market, it required the manufacturer to issue additional warnings to patients. It also required additional study. And that’s why celecoxib is back in the news this week. The results of the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen) trial were released. And the news is good for celecoxib.

Results suggests lower cardiovascular disease risk — and fewer side effects — than expected

The PRECISION trial is a carefully designed and powerful study that analyzed the impact of celecoxib on cardiovascular disease. The study spanned 926 medical centers in 13 countries and enrolled more than 24,000 patients with two of the most common types of arthritis (osteoarthritis and rheumatoid arthritis). Each study subject had a higher than average risk for cardiovascular disease due to a history of high blood pressure or high cholesterol.

Study subjects were divided into three groups who took anti-inflammatory medications every day: one group took celecoxib, one group took ibuprofen, and the last group took naproxen.

Study subjects taking celecoxib in moderate doses were

  • no more likely than those taking ibuprofen or naproxen to have a fatal or non-fatal heart attack or stroke
  • less likely than those taking ibuprofen or naproxen to have significant gastrointestinal problems, such as serious bleeding
  • less likely than those taking ibuprofen to have kidney problems or hospital admission for high blood pressure.

What does this mean for you?

It’s rare that a single study provides a definitive answer or changes practice overnight. But this was a large, well-designed, and expensive study that is unlikely to be repeated any time soon. And, another study of lower-risk people came to a similar conclusion just last year.

Still, questions may yet come up regarding:

  • The lack of a placebo group. As suggested by some prior research, it is possible that all three of the drugs used in this study increase the risk of cardiovascular problems; without a control group, it’s impossible to say.
  • Dosing. Study subjects were allowed to take up to 400 mg/day of celecoxib if they had rheumatoid arthritis but only 200 mg/day if they had osteoarthritis. In real life doctors may prescribe a wider range of doses.
  • Reason for treatment. This study only included people with rheumatoid arthritis or osteoarthritis. The results might be different if people with other conditions had been included.
  • Other medical problems. The risks and benefits of celecoxib in people with other medical problems (such as significant kidney disease) are uncertain because this study excluded them.
  • Other medical treatments. All patients in this study took a medication to protect the stomach; outside of studies, that’s not always the case.

While these issues are valid, I think this study does provide a significant measure of reassurance regarding the cardiovascular risks of celecoxib. And it may encourage doctors who thought the drug was too risky to prescribe it more often.

This new research shows in a dramatic way why “more research is needed” is not just a tagline at the end of so many medical news stories. And in the case of celecoxib, the result of the additional research is good news indeed.


  1. M Peled

    I use Curcumin disolved in olive oil. Perhaps not very medical approved but it did wonders for me.

  2. Bob

    I think study honesty and limitations is a good point to clarify upfront as the future for all credible health websites will be disclosure. The problem with any study’s conclusion is limitations and cost. The more we spend the more we will know but that is a luxury we don’t seem to have and so people must use common sense and wisdom to make their own decisions taking into account their particular circumstance and ability to become informed. I think it would be more helpful to line up people’s life styles and health experience against a selection of possible remedies so that people can see that they have choices. For example I read an advert at a Pharmacy that said that there is no cure for diabetes. They were trying to bring attention to monitoring devices. In truth there is no pharmaceutical cure but there is a diet cure for type 2. The advert was half truthful only and this is not helpful in the long run. There clearly is a necessity for monitoring devices for a particular lifestyle person in mind but not for all. Advice should be given with different types of people in mind.

  3. Amachrcger

    The post is very nice to visible and excellent to provide the wonderful tips to the public.

  4. Richard Christenson

    This article does not specify the number of participants, gender balance, age balance, genetic/racial balance, or the duration of the study. Nor does it discuss the funding sources or the entity collecting and analyzing the data. What was the dropout rate of originally enrolled, for instance? These are all issues (and there may be more) which need to be considered when deciding the applicability to any individual. By the way, what medication was used to protect the stomach?

    • Lori Z. May

      Excellent, necessary points were raised by you. Variables were either negligently or deliberately omitted.
      I have a personal grudge against Celebrex, only based on one person’s experience, and therefore having no scientific validity. But, what he went through with sudden painful swelling of his legs, right after beginning a Celebrex prescription! Wouldn’t want anyone else to go through this. I would caution others to seek an alternative to jeopardizing their leg veins’ ability to function properly. We immediately informed his doctor, but were told there was no connection between the sudden onset of his symptoms, and the date of beginning the Celebrex. He believed his doctor. His doctor believed the pharmaceutical company. The patient continued taking the Celebrex and the swelling and pain in his legs increased. Even after he stopped taking the Celebrex ,and changed doctors, the swelling in his legs continued for years. He had to have help to put on compression stockings every morning. He eventually developed fluid retention in his lungs, congestive heart failure. This is only anecdotal evidence, but it’s still true.

  5. vicki Lindner

    Iyengar yoga done with expert instruction consistently has helped my n osteoarthritis in Basel thumb joints and knees. Years and years ago I was told my thumb joints were bone upon bone. I took viox for awhile…After a million down dog asanas my hands are fine most of the time…for arthritic kneecaps sitting in virasana and doing yoga style squats help a lot. Movement is the secret but it has to be the right kind of movement done with appropriate props.

  6. Sarabjit Romana

    Acupunture works really good to reduce inflammation/ pain. According to my practice of 10 years Acupuncture and chinese Medicine is very very effective holistically treating the patient from root cause with no or fever side effects. After successful Acupuncture treatments , most of patient actually do not need any inflammatory drugs. As mentioned in above comment that taking R Alpha lipioc acid, turmeric, ginger ,garlic etc are good alternatives. Even supplements like Vit D3, magnesium and omega3 are good health.

  7. Don Carlos Dunaway

    In Harvard Health’s words, “…this was a large, well-designed, and expensive study that is unlikely to be repeated any time soon.”
    It’s good that you point out some of the deficiencies of the study; it’s bad, very bad, that you give the manufacturer a pass when from the first word of your account it was evident even to this layperson that the study was indeed well-designed — to carefully sidestep any possible bad news. The manufacturer clearly knew what to avoid in the study, as if they had previously done multiple small-scale studies to learn what to exclude.
    Shame on Harvard Health!

  8. Mrs. C. McIntyre

    My biggest concern is a comparison between aspirin and celecoxib.
    I do have the risk factors of high cholesterol and big family history
    of CV problems. I take aspirin for arthritis pain and always have,
    without any side effects. The question for me has always been whether
    celecoxcib or aspirin works better-but no one has ever tested those
    two against each other. Has that ever happened and I missed it?
    I take Protonix 40 mg bid, so I’m ok there. Can someone discuss
    this, please? Thank you.

  9. A. Fried

    I am wondering how much better a study using a control would be. On a scale of 1to 10, how would a research trial team rate the controlled trial over the non-control trial?? I would guess that a non-control trial would border on NOT being scientific.

  10. Roger Charlesworth

    If you want to control inflammation, which you should, then why not use R-alpha lipoic acid as prescribed by the German health establishment? I have just cured my own case of intercostal neuralgia plus Amla fruit extract in two weeks after suffering for over 3 months. Turmeric and black pepper is also a great anti-inflammatory.

  11. Dan McCrory

    Was Meloxican tested? Is it considered an “anti-inflammatory ” drug? I was prescribed it for ostio-arthritus.

  12. Andrew Goldstein

    I would like to see Cox-2 inhibitor safety and efficacy compared with dietary/physical changes or anti-inflammatory supplements like curcumin. Of course, these studies will likely not be performed because the profits, compared with drugs like Celebrex, are not adequate. We are in a healthcare system that is too profit-driven.

  13. koyakuttymeletath

    Benefits outweigh the risk.Now i think it is time to rule out exactly there is more benefit will get the patient by using a drug or not.Here Cox-1 or Cox-2 are using to relieve arthritis pain.With out using Cox-1 or Cox-2 the patient can extent his life .Better to keep this medicines under investigation until getting clear picture.

    • Jim C

      I have moderate ostio arthritis of hips and lower spine. I now take low dose ibuprofen (400mg) per day. It relieves the pain everytime I move my hips and greatly improves my quality of life.

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