Aspirin, ibuprofen and stroke

Sometimes when I surf the net looking for things to write about I run across things I don't ordinarily write about but attract my attention because they are especially pertinent to my own health. Here's an example. I recently herniated a disk, for which I took fairly hefty doses of anti-inflammatories. Mostly it was extra strength aspirin but often it was horse doses of ibuprofen. I am also of the age that it makes sense to take low dose aspirin for its anti-platelet effects. There is good data to suggest this is a preventative for heart attack and stroke. Now it turns out I may have been nullifying the heart benefits when I took the ibuprofen:

Stroke patients who use ibuprofen for arthritis pain or other conditions while taking aspirin to reduce the risk of a second stroke undermine aspirin's ability to act as an anti-platelet agent, researchers at the University at Buffalo have shown. In a group of patients seen by physicians at two offices of the Dent Neurologic Institute, 28 patients were identified as taking both aspirin and ibuprofen [Motrin, Advil] (a nonsteroidal anti-inflammatory drug, or NSAID) daily and all were found to have no anti-platelet effect from their daily aspirin. Thirteen of these patients were being seen because they had a second stroke/TIA while taking aspirin and a NSAID, and were platelet non-responsive to aspirin (aspirin resistant) at the time of that stroke. The researchers found that when 18 of the 28 patients returned for a second neurological visit after discontinuing NSAID use and were tested again, all had regained their aspirin sensitivity and its ability to prevent blood platelets from aggregating and blocking arteries. The study is the first to show the clinical consequences of the aspirin/NSAID interaction in patients being treated for prevention of a second stroke, and presents a possible explanation of the mechanism of action.

The Food and Drug Administration currently warns that ibuprofen might make aspirin less effective, but states that the clinical implications of the interaction have not been evaluated. "This interaction between aspirin and ibuprofen or prescription NSAID's is one of the best-known, but well-kept secrets in stroke medicine," said Francis M. Gengo, Pharm.D., lead researcher on the study. "It's unfortunate that clinicians and patients often are unaware of this interaction. Whatever number of patients who have had strokes because of the interaction between aspirin and NSAIDs, those strokes were preventable." (HPNOnline)

It was a pretty well kept secret from me, I will admit. It turns out that there is an interesting time-action effect here. Both ibuprofen and aspirin will interfere with platelet aggregation for 4 - 6 hours when taken alone or with aspirin. This is the good effect, the one that inhibits clot formation. That means if you take the combo once a day or ibuprofen alone you are unprotected for the remaining 75% of the 24 hour cycle. But a dose of aspirin alone will affect platelet aggregation for 72 - 96 hours. The effect apparently doesn't cumulate or else we would all bleed out on daily dosing.

Gengo, the lead researcher of the UB study, made another interesting observation. Aspirin is pretty cheap but if you want to pay a lot more for pretty much the same protection, Big Pharma has a solution. They make a drug, Aggrenox, designed for stroke patients to prevent a subsequent stroke, precisely the situation studied here. This expensive item is a combination of aspirin and an extended release agent, dipyridamole, that does the same thing. The combo is alleged to be slightly better, on average, than aspirin alone, but the dipyramole has a common side effect when people start taking it. It causes a headache. According to Gengo:

" . . . some physicians, pharmacists or physician assistants tell patients to take a Motrin so they don't get a headache. This likely would negate the effects of the aspirin and extended release dipyridamole. Those patients might as well take this expensive drug and flush it down the toilet."

Even flushing it down the toilet does some good, however. It still enriches Big Pharma and may make the drug available to the rest of us at no cost -- in our drinking water.

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If the anti-platelet effect of ibuprofen lasts 4-6 hours, what would be the effect of advising patients to take ibuprofen 4-6 hours before their aspirin?

A question on a more basic level: in high school I remember going around asking various science teachers etc. if it was safe to take acetaminophen after taking ibuprofen or vice versa, since the one taken at home had not done the job. Eventually someone looked it up and told us, IIRC, that you could take either aspirin or ibuprofen with tylenol, but you shouldn't take aspirin with ibuprofen. The general sense I got was that aspirin was the least combinable.

Was that incorrect? Or is it that an 81 mg dose of aspirin isn't large enough to make the negative outcomes likely?

(We weren't technically allowed to take any drugs not provided by the nurse during school, but most teachers looked the other way as long as they had plausible deniability, knowing that teenagers could very well medicate their own headaches, colds, and cramps, and having better things to do than stop us from using OTC drugs.)

this is exactly why I don't ever mix drugs...nor will I ever mix beer with wine ever again (I learned that bitter lesson in my early 20s). Also, you should always, always question your doctor about everything he/she tells you or prescribes you. You gotta treat doctors almost like a lawyer. If a lawyer tells you its a nice day, look out the window. If a doctor tells you this drug is ok to take with that drug, talk to the pharmacist.

By pauls lane (not verified) on 17 Mar 2008 #permalink

It should also be observed that virtually all common NSAIDs inhibit chondrocyte activity in vivo, something that will not work out well if you have cartilaginous tissue injuries which need to heal.

A few years ago, after vigorous sustained exertion, the tendons of my forearms hurt. Spoke to my GP. "Tendinitis. Take NSAIDs and take it easy."

I did both faithfully. No resolution in quite some time.

Did my own reading. The GP's recommendation was textbook. But could the textbooks be wrong? Ah! Those NSAIDs might be counterproductive.

Discontinued NSAIDs. Substituted large amounts of raw materials for cartilage synthesis. Continued to take it easy. Symptoms began to resolve within about two weeks' time. They have not returned.

If I had stuck with my GP's advice, I literally would never have gotten well. I'd very likely still be chugging down large and potentially adverse levels of NSAIDs and I'd still be injured.

I see my GP less and less. I don't need to pay a stack of money to be given bad advice, which is the lion's share of what I receive. If the prescription racket were busted open, and if I could just directly buy the handful of things for which I now have to be scripted, I'd see him perhaps once every three years. And my health would be, based on demonstrable empirical evidence, the better for it. Health care cost containment advocates, take note.


This aspirin/ibuprofen thing actually has a rather
elegant explanation. Ibuprofen is a reversable
inhibitor of platelet function: once the drug is
cleared from the system by the kidneys (a few hours),
the platelets regain their procoagulant (clotting) abilities.

Aspirin is an irreversible inhibitor of platelet
function: once the platelets are exposed to aspirin
in the blood, they're down for the count (approx.
48 hrs - 2 days). New platelets have to repopulate the
blood from their source (bone marrow) for the platelet
clotting activity to be restored. This takes 2-3 days
rather than a few hours to get the platelet
function back to normal.

The ibuprofen & aspirin compete for the same sites
in the platelet. If the Ibuprofen gets there a
little ahead, it is, in a sense, protecting the
platelet against the permanent knockout the aspirin
would provide. So - the advice not to mix them.

If you want to take both drugs, do as I do. I take
a low dose aspirin as soon as I get to the bathroom
in the morning. After shower, dressing and breakfast,
I'm free to take ibuprofen for it's anti-inflammatory
effects knowing the apirin has knocked out the
new platelets that have accumulated since the morning

By FattyLittleClot (not verified) on 17 Mar 2008 #permalink

FLC: That's a great explanation, consistent with the facts. It makes a lot of sense. Much appreciated.

Also regarding aspirin: I was told by a chemist years ago that, contrary to popular "wisdom," it is NOT advisable to drink milk within 30 minutes of taking aspirin.

The explanation was that the milk acted to convert the aspirin to a far more acidic form, thus making it far more likely to contribute to burning of the stomach lining.

I don't remember the details (but it made sense at the time), so it would be interesting if the reasoning behind this could be explained too. (Thanks for the explanantion of the timing of ibuprofen and aspirin!)

WOW, FLC can you do more posts like this? What you wrote made more sense to me than just about anything else I've ever read in regards to the aspirin debate.

Why is this news? Is it because the 'why' has finally been discovered? I've known not to mix aspirin with ibuprofen for years. Granted I didn't know why I shouldn't (thanks FLC I do now) but when my daughter was in her early teens even she knew it. In fact she is the one who told me not to mix them. I listened, because her interests in those days were school, NSYNC, Backstreet Boys, boys in general, pimples, and brushing her hair a couple of thousand strokes an evening. I figured with this list of compelling interests, for her to know and advise not to mix aspirin with ibuprofen I needed to pay close attention.

By pauls lane (not verified) on 18 Mar 2008 #permalink