aspirin bottle and bottles of Motrin IB (ibuprofen) and Advil

Pain relievers like ibuprofen, indomethacin, meloxicam, naproxen and piroxicam have been popular for decades. Tens of millions of people take these non steroidal anti-inflammatory drugs (NSAIDs) daily to ease sore joints and relieve a variety of aches and pains. This reader wants to know if there is a connection between ibuprofen and heart attack.

Q. I have just read about a study that shows pain relievers can lead to heart attacks. It said that the ones they tested all have the same risk. At what dose do complications kick in?

I take an ibuprofen (200 mg) almost every day to ease back and hip pain. Sometimes I take an additional dose. In addition, I take a 325 mg aspirin for my heart. Am I asking for heart trouble at these doses?

A. The PRECISION trial you read about showed that celecoxib (Celebrex), ibuprofen and naproxen all posed about the same risk of heart attacks (New England Journal of Medicine, online Nov. 13, 2016).  This has been interpreted as good news by those who funded and supervised the study.

That’s because some experts feared that celecoxib might have fared far worse than traditional NSAIDs like ibuprofen and naproxen when it came to heart attacks and strokes.

The COX-2 Calamity:

Do you remember the Vioxx (rofecoxib) debacle? Before Vioxx and its cousin Bextra (valdecoxib) flamed out, there was great hope for COX-2 inhibitors. NSAIDs like diclofenac, ibuprofen, meloxicam and naproxen are not very selective in how they work. They block two enzymes, COX-1 and COX-2, that produce prostaglandins. These are hormone-like compounds that show up when we sprain an ankle, break an arm or develop arthritis.

Prostaglandins do contribute to pain and inflammation but they also play a critical role in protecting the body from assault. For example, one prostaglandin called prostacyclin keeps the sticky part of blood called platelets from clumping together to form dangerous clots. It also dilates blood vessels. Prostaglandins also protect the stomach lining from damage.

When people take NSAIDs to calm pain they often end up developing indigestion or stomach ulcers. That’s because of reduced prostaglandin production from the COX-1 enzyme. Drug companies thought that if they could just block COX-2 they might ease pain without causing stomach upset.

Doctors were excited when researchers developed compounds to block COX-2 more selectively. By allowing COX-1 to produce protective prostaglandins, they anticipated that patients would get pain relief without GI ulceration from medicines like Bextra, Celebrex or Vioxx. The commercials for this new class of pain relievers made them seem like wonder drugs. People with arthritis were dancing, ice skating, and doing martial arts.

Unfortunately, a Vioxx study produced an unexpected outcome. The drug produced an unacceptably high rate of cardiovascular complications (New England Journal of Medicine, Nov. 23, 2000). One FDA safety officer estimated that more than 100,000 Americans might have suffered a heart attack or stroke as a result of taking the drug.

Because Celebrex was a similar drug it became suspect by association. Like Vioxx, Celebrex selectively blocked COX-2. That’s why a large study was started to see whether this COX-2 inhibitor was as dangerous as Vioxx.

How Precise was PRECISION?

This study seemed huge. It involved 24,081 arthritis patients. The subjects were divided into three groups. One third got Celebrex. Another third got ibuprofen and a third group received naproxen. Some concerns have been raised about the PRECISION study. That’s in part because so many people dropped out. By the end of the trial 16,658 had bailed. That’s 69%. When so many people pull out of a study it becomes harder to interpret the data.

That said, Celebrex did not fare worse than ibuprofen or naproxen when it came to heart attacks. But it also did not perform better. In other words, all NSAIDs are risky for the heart. Some people may be susceptible to OTC doses of ibuprofen and heart attack.

What About Low Doses?

The dose used in the trial was much higher than the one you are taking: 600 mg of ibuprofen three times a day.

Since you are taking a fraction of the amount tested, the danger is presumably much lower, but probably not zero. Another concern is that ibuprofen and naproxen can undo the anticlotting activity of aspirin. As a result, you might not be getting the expected heart benefit from the aspirin you take.

Celebrex (Celecoxib) and Aspirin:

Celecoxib, on the other hand, does not appear to interfere with aspirin. You may want to ask your doctor if it would be a better alternative than ibuprofen.

We are sending you our Guide to Alternatives for Arthritis for more information on managing ongoing joint pain. Anyone who would like a printed copy, please send $3 in check or money order with a long (no. 10) stamped (68 cents), self-addressed envelope to:

Graedons’ People’s Pharmacy, No. AA-2,

P. O. Box 52027,

Durham, NC 27717-2027

It can also be downloaded for $2 from the website: www.peoplespharmacy.com.

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  1. Barbara
    Albany, NY
    Reply

    Thanks for the info, Joe. Good place to start researching. Just one thing — it’s kind of like ‘what came first – the chicken or the egg.’

    What’s not being mentioned here is the very, very serious damage that inflammation by itself can cause, especially if inflammation is low-grade and long-standing – body-wise damage – lungs, liver, kidneys, etc. It’s a difficult choice. I wish some of the ‘natural’ remedies worked as well.

    I have a prescription for the gel, but I wonder if that’s not causing the same problems – raising blood pressure, constricting arteries, etc. ultimately, even if it bypasses the stomach. My Rheumatologist (I have inflammatory arthritis) suggested 2 Aleve twice a day and I couldn’t stand the heartburn and stomach upset, so I quit using it. However, my foot doctor gave me a prescription for generic Naproxen, 500 mg. which I take once a day on a very full stomach. I have no problems with this, of course at a much lower dosage, but for some reason, this seems to work.

    I have a family history of cardiac problems caused by inflammatory conditions – RA, inflammatory arthritis, allergies, immune-sensitive issues), all of which have led, in and of themselves, to heart disease problems, without NSAIDS – hence my dire need to control inflammation.

    I am in the process of starting a regime of Boswellia, Fish Oil, and Evening Primrose oil. I know these also pose the danger of thinning the blood too much, but my platelet aggregate count was/is high (due to chronic, low-grade inflammation), so I think the oils may even help some. I’m just not sure of the truth with a lot of these ‘studies.’ That being said, I sure don’t want to risk it so, as I mentioned, I’m looking into alternatives, while maintaining a low dose of Naproxen. I know if you go to a pain ‘specialist,’ you get treated as if you were an addict and the effects of the drugs they give you are surely not worth it. I sincerely hope these natural alternatives help. As in life, “ya pay your nickel and you take your ride.” Thanks for the research leads. We can send people into outer space, but we somehow can’t make a painkiller without danger!!

  2. Barbara
    Reply

    In my readings regarding the use of Ibuprofen, I have often noted the “association” between Ibuprofen and the incidence of heart attacks, but I have never found out the direct causal effect. I have read where the drug causes stomach problems, interferes with other drugs such as Losartin, but I have never read about a PROVEN direct connection. There have been studies, yes, where the incidence of heart attacks are higher in individuals taking drugs such as Bextra and Vioxx, but I believe that it’s a ‘stretch’ putting the same cardiac effects on all forms of Ibuprofen. I have also seen ‘studies’ touting Ibuprofen’s PROECTIVE effect in Alzheimers. So what is the truth? And, most importantly, what is science/medicine offering in the way of alternatives? Lots of people (myself included) NEED to take minor painkillers for arthritis and other ailments, so what are we being offered in substitution? The Ibuprofen controversy is beginning to sound to me like the time we were all told that coffee would ‘harm’ us, if not ‘kill’ us. Now coffee is deemed beneficial. Yes, as with all things, moderation is the key — too much of anything can be harmful, but what are we being offered when a painkiller is a ‘must?’ I’ve been taking Ibuprofen for years will no ill effects — I moderate my dosage, take it with food, take it away from medicines with which I know it will interfere. Personally, I need absolute proof that Ibuprofen and its ilk ACTUALLY causes heart attacks and I don’t seem to be able to find that ABSOLUTE proof — just a lot of ‘guessing’ by the medical community — “don’t take it, just in case.” However, what else is there?

    • Joe Graedon
      Reply

      Barbara,

      You are quite right that there are not a lot of alternatives to NSAIDs. Have you ever considered topical NSAIDs? Although they are not available OTC in the U.S., you could ask your doctor about a prescription for something like Voltaren Gel. Such products may be less problematic than oral NSAIDs.

      As for the mechanism regarding cardiovascular complications…it’s complicated! NSAIDs like ibuprofen are considered “nonselective.” That means they block the enzymes COX-1 and COX-2 which make prostaglandins. These hormone-like compounds serve a variety of functions in the body. They are responsible for pain and inflammation, but they also protect the stomach lining from irritation and ulcers. Prostaglandins (prostacyclin in particular) prevent blood clots and dilate blood vessels. When NSAIDs block formation of prostacyclin there is an increased risk of heart attacks and strokes. The FDA has very clear warnings in this regard that are based on numerous studies. I do not think there is any doubt that NSAIDs have adverse cardiovascular risks.

      Even if the overall risk is small, so many millions of people take such drugs daily that the numbers mount up. Part of the trouble is that if someone with aches and pains of arthritis dies of a heart attack or stroke everyone chalks it up to age or some underlying health problem that wasn’t identified. Proving that the NSAID caused the event is almost impossible. Older people do die of heart attacks and strokes even if they are not taking an NSAID. That said, the evidence does suggest that NSAIDs up the risk.

      All you need to do to see the data would be to Google “PubMed.” When you get to the National Library of Medicine search NSAIDs and Cardiovascular and see what you get. There are so many entries you could spend weeks reviewing the scientific literature on this subject.

  3. Gale
    Pennsylvania
    Reply

    Do you know if, in this study, naproxen statistics were separated out? I think I read that it was more likely to cause problems than ibuprofen.

  4. Candy
    NC
    Reply

    I was prescribed 800 mg of ibuprofen 3x a day for a knee injury. I went to a new primary doctor two months later, and my blood pressure was 188/100. It is normally 120/70. Then I read that ibuprofen can cause high blood pressure.

  5. Melanie
    CA
    Reply

    Years ago a pharmacist warned me about Aleve; my go-to OTC.
    A few years later my then cardiologist said to only take aspirin or Tylenol. I’ve since discontinued aspirin because Dr recently prescribed Eliquis (5 mg BID), but am concerned about taking Tylenol to relieve debilitating arthritis pain.

  6. Michael W Yorke
    NC
    Reply

    I’d suggest she could use 81mg (baby aspirin) instead of 325. I think the large majority of people using aspirin for heart benefit use 81mg.

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