June 10th, 2010
09:06 AM ET

Pain relievers connected to heart deaths

By Elizabeth Landau
CNN.com Health Writer/Producer

Common pain medications are associated with higher risks of heart-related death in healthy people, a Danish study finds.

The research, published in the journal Circulation: Cardiovascular Quality and Outcomes, a journal of the American Heart Association, is the first to report on specific cardiovascular risks among healthy people.

Study authors looked at the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in Denmark, based on records of more than 1 million healthy people over age 10 from 1997 to 2005. About 45 percent of people in the study took NSAIDs at least once over that time period, and those who did usually took the drug in low doses for about two weeks.

They found that ibuprofen - the main ingredient in Advil and Motrin - was associated with a 29 percent greater risk of fatal or nonfatal stroke, compared with people who did not take a prescription NSAID.

Diclofenac, marketed under various brand names including Voltaren and Cataflam, was linked to a 91 percent heightened risk of cardiovascular death. In the United States it is available by prescription; other countries sell it over the counter.

Rofecoxib, which was once sold in the United States as the controversy-mired Vioxx, was associated with a 66 percent greater risk of cardiovascular death in this study. Merck & Co. voluntarily recalled Vioxx in 2004 because of cardiovascular safety concerns, and has not reintroduced it.

Researchers found a two-fold higher risk of heart attack among people taking the highest-level doses of diclofenac and a three-fold risk with the highest does of rofecoxib.

Naproxen, on the other hand, was not associated with heart problem risks in this study. This drug is commonly marketed in the United States as Aleve. Researchers could not conclude anything about the risks of celecoxib, sold as Celebrex in the United States.

Pfizer Inc., maker of Advil and Celebrex, said in a statement that Advil is safe and effective when used according to the label instructions on the package, and the FDA has stated that the benefits of Celebrex outweigh the potential risks in properly selected and informed patients, Pfizer's statement said. McNeil Consumer Healthcare, maker of Motrin, echoed that "When used as directed, ibuprofen is safe and effective." Novartis, maker of Cataflam, said in a statement that the company is aware of the study, and that it "does not change the favorable benefit to risk assessment for diclofenac when used as directed."

"All prescription NSAIDs carry the same cardiovascular warning and may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal," Pfizer's statement noted.

The Danish study has implications for the U.S. population also, researchers said. The American Heart Association advised in 2007 that NSAIDs, except aspirin, for chronic pain upped the risks for heart attack and stroke, which is consistent with these findings.

Talk to your doctor if you have concerns about the medication you are taking.

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soundoff (62 Responses)
  1. Mike B

    If we read the article & the references, specifically #20, we see that repeated studies have now shown that naproxen, which lasts for up to 12 hours & is available generically, is the only NSAID besides aspirin that not only doesn't cause cardiovascular deaths but prevents them. Why would this article include the drug companies comments that contradict repeated studies? Why allow them to say all nonaspirin NSAIDs are equally bad, when reference #20 in this Danish study points to the exact chemical mechanism that aspirin & naproxen share that other NSAIDs don't that appears to prevent cardiovascular death?

    June 10, 2010 at 09:36 | Report abuse | Reply
  2. Mitchell Kirby

    This study is purely correlational. A large proportion of the findings are due to the fact that people who are taking these medicines are probably in lower health than those who are not. Thus, people taking these medicines selects for a group with a higher risk of these disease, the medicine itself probably does not cause the disease.

    June 10, 2010 at 09:44 | Report abuse | Reply
  3. marianna

    These studies were done in healthy people. The people who have high blood pressure or heart disease may be at an even higher risk of adverse effects of the drugs like Motrin, Advil or Celebrex on the heart.

    Actually American Heart Association recommends to stop drugs like Motrin or Celebrex immediately after a heart attack.


    June 10, 2010 at 10:07 | Report abuse | Reply
  4. Sierra Hennessy

    Dr. Gupta,

    I read this article with interest and have a concern. What about all the women who take Motrin or Advil for monthly symptoms of PMS? I take Motrin frequently for headaches, which I get weekly and sometimes daily because of a brain trauma. I have high genetic factors for heart attack. Is this a serious enough issue that I should discuss it with my doctor?

    June 10, 2010 at 10:08 | Report abuse | Reply
  5. Ursula

    According to this article, It is better to take Aleve.

    June 10, 2010 at 10:18 | Report abuse | Reply
  6. ECS

    So just to be clear...this does not apply to aspirin. Correct? My understanding is that pure aspirin actually had the opposite (heart beneficial) effects.

    June 10, 2010 at 10:25 | Report abuse | Reply
  7. hd brown

    voltaren, that's scary. i used that a bit but it made me nauseous. they give that out like fishes & loaves at the back pain clinic. no wonder (any of us have survived thus far).

    June 10, 2010 at 10:30 | Report abuse | Reply
  8. EJH

    This is another flawed retrospective study inspired by the need to publish or perish and the abundance of data collected that is massaged into a headline grabbing outcome. It relies on self reporting of taking over-the-counter NSAIDs. Additionally there was nothing in the study to look at why these "Healthy" people were taking the drugs or what other risk factors they had like smoking or obesity. There is no definition of "healthy" and people who need to self medicate may not be healthy at all. These people were probably not healthy, and the conclusion that taking the drugs caused their demise is a post hoc – proctor hoc fallacy of reasoning. Nothing in the study looks to determine if these "healthy" people had underlying problems and the true cause of death. It's sad that so many people that can be helped by these medications are now made afraid of them.

    June 10, 2010 at 11:02 | Report abuse | Reply
  9. karpo

    If the 1 million people were a healthy population, then very few of them had a stroke. Since only just a few people had strokes, the seeming 29% greater risk of stroke is probably not statistically significant. Pharmaceutical companies pull stunts with statistics all the time, to justify the effectiveness of their medications. If you look at studies involving the statin drugs, you will find similar tricks used.

    June 10, 2010 at 11:21 | Report abuse | Reply
  10. Katey

    Every single pill you put in your mouth has an ill-health consequence eventually. We are such a pill happy society; perpetuated by Doctors and Pharmaceutical companies. Try eating your vegetables and fruits and lots of fish and water and take a walk everyday. Bye bye medicines!

    June 10, 2010 at 11:26 | Report abuse | Reply
  11. Park Adam

    I agree with Mitchell Kirby, the so called Treatment-by-Indication Bias.

    In addition this is a observational study which only shows association, not causality.

    Articles like these are ok for those with clinical science acumen, but when published like this, on a website generally accessed by lay folks, it may send the wrong message to the public.

    Unfortunately the general public can't differentiate between an observational epidemiologic approach vs. prospective internventional studies and where the strengths vs. limitates of each study type is, as in the confounded-by-indication nature of this study.

    So, although this article is reasonably fair-balanced, I think this can be sending the patients to the doctors for reasons that are not clinically sound and may reflect an un-ethical alarm by the media (CNN in this case). Just as doctors take an oath to "do no harm", so should the media.

    Interpreation of the data should be left the authorities and approriate alarms sent by them.

    June 10, 2010 at 11:26 | Report abuse | Reply
  12. Justin

    This is why marijuana needs to be legalized. There are absolutely no harmful side effects, yet we sit here and worry which pain killer will least likely kills us. Pot kills no body, time for america to wake up. You too Dr. Gupta

    June 10, 2010 at 11:50 | Report abuse | Reply
  13. JGB

    What about Lodine/Etodolac? Also, how these NSAIDs cause problems has always been unclear to me.

    June 10, 2010 at 11:54 | Report abuse | Reply
  14. antifool

    Mitchell, glad you are the foremost expert and have conducted your own tests to disprove these tests that were published. Please provide a link to your research so we may all be so enlightened as you.

    Sierra. Common sense dictates you should ask your doctor, not Gupta, regarding this.

    June 10, 2010 at 12:01 | Report abuse | Reply
  15. ESP

    Mitchell is absolutely correct. The study is correlative, not causative. One very plausible link is that the medications are anti-inflammatory, so those taking these meds have more inflammation. We also know that inflammation plays a prominent role in vascular disease.

    June 10, 2010 at 12:02 | Report abuse | Reply
  16. A. Mill

    The article forgot the most important detail.

    These risks (with the exception of diclofenac) are *highly* dose dependent. Overall it may seem that naproxen is safer than ibuprofen, but unless you're taking more than 1200mg for 14+ days, the risk for cardiovascular events is essentially the same.

    June 10, 2010 at 12:11 | Report abuse | Reply
  17. aspirin

    Aspirin initially will cause your blood to thin decreasing your blood pressure, but long term dosage actually does the opposite, raises your blood pressure.

    June 10, 2010 at 12:15 | Report abuse | Reply
  18. American Me

    Wow. I always have back issues and take ibuprofen like candy. No more. More ice and massage I guess.

    June 10, 2010 at 12:15 | Report abuse | Reply
  19. Katsky

    Sadly, I can't even tell when I've taken naproxen (Aleve). In my experience, it does not work.

    June 10, 2010 at 12:25 | Report abuse | Reply
  20. teb

    So aspirin and naproxen are safe? Should I not buy Advil now? I always thought Advil worked better for my pain. But I have heart and stroke issues in my family history and would prefer to be safer than sorry.

    June 10, 2010 at 12:30 | Report abuse | Reply
  21. ubo

    I was worried when I saw the title of this, but after reading it, pretty revealed. I take a lot of aspirin for pain and I was worried, but thankfully it apparently has no negative effects like that. Now only if it didn't put holes in my stomach and liver....only slightly kidding.

    June 10, 2010 at 12:33 | Report abuse | Reply
  22. Anna

    Naproxen, on the other hand, was not associated with heart problem risks in this study. This drug is commonly marketed in the United States as Aleve. Researchers could not conclude anything about the risks of celecoxib, sold as Celebrex in the United States.

    June 10, 2010 at 12:36 | Report abuse | Reply
  23. Michael S

    @Mike B
    Well, if you read the article, the study looked at Aleve and the associated generics, which is why it is included in this new report. It also states a couple of times, Naproxen Sodium and Aspirin are the only NSAIDs not associated with an increase in heart problems.

    See above

    Don't forget all NSAIDs can be hard on the liver/kidney/stomach.

    June 10, 2010 at 12:41 | Report abuse | Reply
  24. kay white

    I've been taking diclophenac for close to 7years (daily) at 100mg. Should I be worried. I do have heart problems in my family. I take this medicine for arthritis.

    June 10, 2010 at 12:47 | Report abuse | Reply
  25. Katie

    Guess the best advice for many people is to stop reaching for that pill bottle for every little ache and pain and learn how to tough it out. I'm not talking about people with migraines or bad arthritis or other diagnosed problems, but those who routinely down a pill for minor things that could be preventable or that go away all by themselves.

    June 10, 2010 at 12:49 | Report abuse | Reply
  26. M.L. Hurley

    I have severe arthritis in both knees and lower back so I have been taking Diclofenac (75mg a day) for probably 4 or 5 years. What would be a safe alternative to Diclofenac?

    June 10, 2010 at 12:51 | Report abuse | Reply
  27. Jeff

    Mitchell Kirby comments that the "study is purely correlational. A large proportion of the findings are due to the fact that people who are taking these medicines are probably in lower health than those who are not."

    What he misses is that while the patients may have been taking the medications because of other health problems, and thus are not a representative sample of the general population, those who took certain NSAIDs (e.g., ibuprofen) had a much higher risk of serious cardiovascular events than patients who took other NSAIDs (e.g., naproxen).

    Unless one wants to hypothesize that other factors strongly determined the choice of which NSAID was taken by different patients then the conclusion is very strongly supported by the studies. Note that the drug manufacturers do not deny the conclusion but rather suggest that the increased risk is still within the general parameters of what they consider to be "safe".

    June 10, 2010 at 13:01 | Report abuse | Reply
  28. DNA

    I think I will not take Advil anymore.

    June 10, 2010 at 13:06 | Report abuse | Reply
  29. sammie

    Is aleeve ok for pregnant women? How about infants and toddlers taking motrin for their cold and fever is that dangerous too? What about tylenol? Isn't there an issue with that too? So what is really safe for people to take?

    June 10, 2010 at 13:11 | Report abuse | Reply
  30. knez011

    Naproxen sodium (Aleve) can increase blood pressure considerably. I work out 6days a week and have been using Aleve for years (one before each workout – gym or long distance training run). I switched from Aleve to Tylenol max strength and within two weeks my blood pressure went from 135/90 down to 125/80. It's been like this for several weeks now.

    June 10, 2010 at 13:12 | Report abuse | Reply
  31. chuck

    I have arthritis.

    I'm confused about Celebrex in this study.

    Was Celebrex studied here and didn't show any problems or was it NOT included in the study??

    Also, is Aleve upsetting to the stomach after a few days/weeks of intake (like advil or asprin)??


    June 10, 2010 at 13:13 | Report abuse | Reply
  32. CR

    Why not stick to good old aspirin? Safe and effective, but the formula is public domain (low profit). I think the consumer has been hoodwinked.

    June 10, 2010 at 13:13 | Report abuse | Reply
  33. Skunco

    So what does this mean? People who feel sick engough to need nsaid's are sicker over-all than poeple who feel fine and dont take nsaid's? Thats what I get out of this stupid report.

    June 10, 2010 at 13:15 | Report abuse | Reply
  34. bennett

    I will testify to this –

    taking over the counter ibuprofen per the instructions on the bottle – garden variety – triggered a GI tract bleed out that nearly killed me –

    Thanks FDA for protecting us from Marijuana (sic) and allowing Statins, NSAIDs and other toxic regimes to become standard parts of our diet. I guess we will also now be looking overseas for the direction of health care, whether research or just cost efficiency... BRAVO!!

    June 10, 2010 at 13:22 | Report abuse | Reply
  35. Dwayne

    When I was only 21 years old I took Advil brand Ibuprofen at the highest dose according to the label for 2 days straight and had a mild heart attack. The doctors ran all the tests they could–I am healthy weight and had an otherwise healthy heart...no cholesteral problems at all. I know it was from taking this medication for headache.

    June 10, 2010 at 13:26 | Report abuse | Reply
  36. Bill

    I just had to start taking a blood pressure medicine recently and the only common pain reliever *not* listed in the "don't take these" list is acetaminophen. Even aspirin and naproxen were listed.

    June 10, 2010 at 13:26 | Report abuse | Reply
  37. Barbara

    I take Tramadol and gabapentin. I have for years and i don't see it stopping anywhere soon due to chronic back pain. Has anyone heard of problems associated with them?

    June 10, 2010 at 13:35 | Report abuse | Reply
  38. Jennifer

    Odd, because my Naproxin bottle says that it can in fact cause heart problems.

    June 10, 2010 at 14:01 | Report abuse | Reply
  39. Patrick

    For what its worth, I have high blood pressure that is under control with a small amount of medication (Lisinopril). I cannot take ibuprofen, as it makes me feel horrible. The last time I took some was after a large mountain hike. The ibuprofen subsequently broke several vessels in my eyes (my eyes turned blood red) and felt so horrible that I had to get in bed and do nothing for the rest of the evening. I felt like I was going to die, and there was nothing I could do about it. I will never take it again.

    June 10, 2010 at 14:04 | Report abuse | Reply
  40. LetsFixIT

    Im not a medical or Rx profeassional But "Experience Counts"! My legs have been paralyzed for over 25 years, and continuously (expending extra-ordinary) efforts to live a typically active life-sytle(FT job, some travel, single parent, etc) has caused significant wear-and-tear to upper body muscles and joints (constant pain and so on). My Experience with all of these follows: Naproxin (like but stronger than asprin) sooner or later causes serious deterioration of stomach lining (i.e.Bleeding). Vioxx may/caused highly irregular heart beating w/i less than 3 weeks – Quit it Fast! Celebrex was v-good for pain But Serious stomach Bleeding w/i 20 days of prescribed use! All 3 of those sent me to the ER with use as prescribed or LESS!! (I know that I may be sensitive to chemical medications!) I have No Health Problems – just excessive physical actrivitry / effort. Advil & Motrin have been OK (limited daily use 2 or 3) for Years now! MediTation Helps!! STOP the Rx Lobbyists!! and 'Profits First' motives of "ethical drug industry' (OxyMorons) – Lets Get Marajuana DeCriminalized!! (Maby I'll sleep better)! Best-of-Luck! to you.

    June 10, 2010 at 14:06 | Report abuse | Reply
  41. Me

    now i need some pills after reading all this!! 🙂

    June 10, 2010 at 14:07 | Report abuse | Reply
  42. Claudia, Houston, Tx

    "Talk to your doctor if you have concerns about medications" interesting when doctors are recommending these meds and are also in bed with pharma companies. I stopped taking anything for pain other than aspirin and it works for me just fine.

    June 10, 2010 at 14:08 | Report abuse | Reply
  43. Marla

    I have been told to take an aspirin before taking ibuprofen, b/c it counteracts the clotting agents in ibuprofen, which can lead to stroke. I wonder what the results of this study would have been had they monitored those who took aspirin beforehand.

    June 10, 2010 at 14:12 | Report abuse | Reply
  44. Audrey

    I wonder if they controlled for other risk factors, since individuals suffering migraine with aura are already at a higher risk for stroke than the general population. What exactly is meant by "healthy people"?

    I will continue to avoid ibuprofen in favor of naproxen and will encourage others to do the same.

    June 10, 2010 at 14:21 | Report abuse | Reply
  45. dc_doc

    When are physicians (and, arguably, the medical community in general) going to realize that sporadically administering prescriptions like hydrocodone, codeine, and oxycodone with acetaminophen is a hundred times safer than copious amounts of OTC painkillers?!

    Personally, I'd rather a patient take one 5/325 Percocet than 800mg of Ibuprofen or 500mg of Naproxen. It's a hundred times more effective at eiliminating pain, and you can control how much the patient has access to. 325mg of acetaminophen with a mere 5mg of oxycodone or 500mg of acetaminophen with 5mg of hydrocodone is preferable to 800mg of Ibuprofen. Any doctor worth his salt will admit that.

    We have to reevaluate both our OTC and Rx painkiller culture. Doctors need to feel less threatened by Big Brother and patients need to feel like we care more about their pain than the DEA. We all understand there are abusers. That is true of any drug. But, based on what I've seen in practice, I know what excessive amounts of NSAIDs can do to a patient's stomach and kidneys. I haven't one patient with liver disorders from prescribing them ten Percocet or Vicodin when they have acute pain.

    To my fellow physicians: You've been told.

    June 10, 2010 at 14:27 | Report abuse | Reply
  46. Maria

    Justin – your comment on marijuana being safe is so very wrong. Saying marijuana never killed anyone is ignorant. What about the person high on marijuana who drives or operates some type of machinery and causes a major fatal accident? Not only that but with regular or frequent use, it does change brain chemistry causing problems with impulse control, distortion of perception, loss of learning ability/dementia, impaired coordination. It also can cause personality disorders or psychological problems such as anxiety, depression, even schizophrenia. Marijuana causes all the same pulmonary problems that cigarette smoking does such as emphema, cancers and heart disease. Marijuana is addicting unlike NSAIDs which are not addicting. It is more difficult to stop marijuana than NSAIDs due to withdrawal symptoms.

    June 10, 2010 at 14:29 | Report abuse | Reply
  47. AJ

    "They found that ibuprofen – the main ingredient in Advil and Motrin – was associated with a 29 percent greater risk of fatal or nonfatal stroke, compared with people who did not take a prescription NSAID."

    This confuses me because Advil is not a prescription drug it is over the counter. How can you compare Advil to people who "did not take a prescription NSAID" if Advil itself is not a prescription NSAID? What am I not getting?

    Wouldn't you compare a non prescription NSAID to a prescription NSAID instead?

    June 10, 2010 at 14:32 | Report abuse | Reply
  48. Carole

    I was on Diclofenac for several years – I became anemic because I was bleeding in my small intestine. My GI guy said the cure was to stop taking Diclofenac and that it was one of the worst of the arthritis drugs to be on.

    June 10, 2010 at 14:38 | Report abuse | Reply
  49. jenn

    So just to be clear......inflammation causes heart disease, and anti-inflammatories cause heart disease too. That is interesting.

    June 10, 2010 at 14:59 | Report abuse | Reply
  50. dc_doc


    Rx-strength NSAIDs come in higher quantities. Any time you take more than the MDD (which is put on every bottle of Ibuprofen, Acetaminophen, Aspirin, and Naproxen) you're going against medical advise. If you take more than two Advil without your doctor's consent, you are using outside of the MDD.

    Now, if your doctor evaluates you and determines that your condition warrants 500-800mg of an NSAID, then it has to be prescribed. Few doctors will just say, "Take four Advil."

    I would advise people NOT to exceed the MDD on any medication. Those rules are there for a reason. Oftentimes, taking more than the MDD will not only be completely pointless, but counterproductive. If you feel that the MDD or RDA is not adequate, please call your doctor. Don't just pop 4 Advil, please. You can cause irreparable kidney damage with too much Ibuprofen the same way you can cause liver damage with too much Acetaminophen. Aspirin severely affects your digestive/GI system. I've seen it firsthand.

    So yes, there is Rx-strength Acetaminophen, Ibuprofen, and Naproxen.

    June 10, 2010 at 15:01 | Report abuse | Reply
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