For 25 years, daily aspirin for people over 50 has been standard advice from the medical profession. A few weeks ago, the FDA changed its tune, and now recommends daily aspirin only after your first heart attack. I’m sticking with the classic advice. Aspirin is an anti-inflammatory with benefits that include lower risk of dementia and some cancers. The overall reduction in death and disease adds the equivalent of about 2 years of life. Though aspirin causes stomach irritation in some people, you will know quickly if you are one of them, and can try a different NSAID.
What changed? What were they thinking? Although the FDA policy change has been widely publicized and there are several new consumer information pages, I have been able to get no information from them about the primary literature on which they relied.
Reading between the lines, I find hints that the decision was based narrowly on the benefit of avoiding fatal heart attacks vs the cost of stomach bleeding and ulcers. I see no evidence they considered the benefits of aspirin in lowering cancer risk or Alzheimer’s risk. And I suspect that in evaluating the heart benefits, they were looking only at the anti-coagulent effect (short-term) and not the anti-inflammatory effect (long-term). (I wrote about the difference last year.)
According to Robert Temple, M.D., deputy director for clinical science at the Food and Drug Administration (FDA), one thing is certain: You should use daily aspirin therapy only after first talking to your health care professional, who can weigh the benefits and risks.
– FDA Consumer Updates
If “one thing is certain,” it is that this advice is motivated by legal and not medical considerations. How many of us are lucky enough to have a family doctor or GP who keeps up with the literature and drills into the statistics? If today’s doctor had time for such things, his employer would jack up his patient load.
Without seeing the basis for the decision, I can think of only two reasons they might lean in this direction. First, there is a tendency toward “natural medicine”, or trusting the body, or erring on the side of non-intervention. I have argued that this is appropriate in young patients, but that you can’t “trust the body” with respect to diseases of old age. The body is not trying to optimize health; it is programmed to die; so there should be no presumption against intervention. Second is the really cynical possibility that aspirin is not a money-maker for anyone, and damping aspirin prescriptions will increase pharmaceutical profits on statins and other expensive drugs.
Dr Mercola devoted a column to the FDA decision last week. While I respect Dr Mercola and frequently look to him for ideas and leads, I think that in this case he has made a mistake. He lists seven of the studies with worst outcomes, and I don’t think he characterizes them fairly. I can only guess that Mercola has fallen for the natural anti-aging fallacy.
|Study||Mercola’s take-home||My reading of the same article|
|American Heart Journal 2004 (WASH)||Patients receiving aspirin treatment showed the worst cardiac outcomes, especially heart failure||This study compared short-term results only for aspirin compared to more powerful anti-coagulants that are too dangerous to use long-term. All subjects had had a previous heart attack. Differences among the groups were insignificant due to small study size.|
|New England Journal of Medicine2005||Ten-year study at Harvard involving nearly 40,000 womenfound no fewer heart attacks or cardiovascular deaths among women receiving aspirin therapy||Actually, there were 9% fewer heart attacks among women taking aspirin, but this was not statistically significant because the subjects were primarily younger women, so there were few heart attacks in either group.|
|British Medical Journal 2009||Aspirin therapy for diabetics produced no benefit in preventing cardiovascular events||In a meta-analysis of 6 studies, aspirin produced a 10% reduction in heart attacks, but it was not significant because of sample size.|
|Pharmacoepidemiological Drug Safety 2009||Swedish researchers studying individuals with diabetes found no clear benefit for aspirin, but did note it can increase the risk of serious bleeding||Younger diabetic patients who took aspirin had so many deaths from bleeding that it exceeded the benefits in terms of heart disease. For older diabetic patients, the lives saved from heart disease exceeded lives lost to bleeding.|
|Journal of the American Medical Association 2010||Scottish study found that aspirin did not help prevent heart attacks or strokes in healthy, asymptomatic individuals with a high risk of heart disease||6% reduction in deaths from all causes was not significant because of small sample size.|
|Journal of the American College of Cardiology 2010||Patients taking aspirin showed a higher risk for recurrent heart attack and associated heart problems||My interpretation is that subjects taking aspirin had their first heart attack 4 years later than others, and as a result their second heart attack was more likely.|
|Expert Opinions in Pharmacotherapy 2010||British meta-analysis of 7374 diabetics concluded that aspirin does not lower heart attack risk||4% reduction in mortality and 10% reduction in heart attacks was not significant because of small sample size.|
Results from more positive studies
There have been many studies with positive outcomes.
This meta-analysis 2002 covered 287 studies with 135,000 total patients, and overall cardiovascular risk reduction was found in the range 30%, with 17% reduction in mortality.
This meta-analysis (2003) covered 9 studies of Alzheimer’s disease, and found among subjects who had been taking NSAIDs more than 2 years, the risk was down 73%. That is not a misprint, Among subjects taking aspirin, the risk of Alzheimer’s was only ¼ as big.
This meta-analysis (2012) looked at cancer risk and found 25% fewer cancer cases, 15% lower cancer mortality with aspirin.
Just this week, Nicholas Bakalar, writing in the NYTimes reported on a new meta-analysis:
The analysis, published online in Annals of Oncology, found strong evidence that aspirin reduced the risk for colorectal cancer, and good evidence that it also reduced the risk for esophageal and stomach cancers. There were smaller or more variable effects for protection against breast, prostate and lung cancers.
They also found that long-term use was required. In controlled trials, there was no benefit until at least three years of use, and mortality was reduced only after five years. A “baby aspirin” of 75 to 81 milligrams was sufficient, and there was no evidence that larger doses provided added benefit.
Bleeding as a side-effect
A small number of patients have trouble with bleeding and upset stomach, and it is easily determined whether you are among those. If so, stop taking aspirin. The number of heart attacks and cancer cases prevented may also be a small number, but there is no way to know in advance, and I say, if the aspirin isn’t hurting you, take your chances.
History – How did we get here?
Use of willow bark to relieve pain goes back at least to the Egyptians 3,000 years ago. Native American shamans used willow for fevers and headaches. The aspirin molecule was first isolated in the mid-19th century, and synthesized (by Bayer) before 1900. It became the world’s largest-selling analgesic, and has been so ever since.
In the 1960s, biochemical knowledge was still rudimentary, and heart attacks were conceived as a plumbing problem. Arteries to the heart become clogged and blood flow is impeded. Doctors knew that the clogging was exacerbated by the tendency of blood to clot around the fatty deposits that were causing occlusion. So it seemed that anti-coagulants (blood thinners) should lessen the risk of heart disease in the short term. Aspirin was known to be a blood thinner, and assumed to be safe based on its long history.
Beginning in 1971, Peter Elwood and John O’Brien began the first trial of aspirin to see if it would reduce the risk of heart attacks. Early results were positive, indicating a short-term benefit. Early adopters were taking daily aspirin in the 1970s and as experience accumulated, statistics made a convincing case that they were having fewer heart attacks. By the late 1980s, use of daily aspirin to lower risk of heart disease became a standard medical recommendation.
The justification for daily aspirin at the time was based entirely on statistics. It was assumed that the benefit came from aspirin’s anti-coagulant activity. “Inflammaging” was still in the future, but the idea that heart disease was associated with inflammation in the artery wall was just being explored.
It is only in the last fifteen years that perception of how aspirin works has shifted. Aspirin is an anti-inflammatory agent, the prototypical non-steroid anti-inflammatory drug (NSAID). Inflammation is associated not just with heart attacks and ischemic stroke, but also with cancer, arthritis and Alzheimer’s disease. Daily aspirin is associated with lower incidence of all these diseases.
The long-term effects of anti-coagulants on heart attack risk proved to be complicated. But anti-inflammatory action is the most reliable strategy we have at present for reducing risk, not just of heart disease but of all the diseases of old age. Because of shakey ideas about blood-thinning and heart attacks, millions of people were advised to take daily aspirin. Decades later, it was discovered that these people had lower rates of heart disease, dementia, stroke, and cancer, because of the fortuitous happenstance that aspirin is also an anti-inflammatory agent.
Incidentally, all of the five anti-inflammatory agents I listed are also blood thinners (aspirin, ibuprofen, naproxen, fish oil, curcumin). I don’t know enough biochemistry to understand why the two should be related.
Is aspirin better than other anti-inflammatory supplements?
Comparison with ibuprofen and naproxen has been done, but asking only a limited set of questions. Compared to ibuprofen, aspirin is a little more likely to irritate the digestive tract, but less likely to damage the liver. Compared to naproxen, aspirin is not as strong, but safer. I have not seen a comparison with fish oil or curcumin.
It should be possible to define a strength of anti-inflammatory effect, and compare different agents, but I have never seen even that done. Of course, what we would like to see is controlled, long-term human epidemiological studies comparing effects of all five anti-inflammatory agents on four major disease outcomes (cancer, heart attacks, stroke and Alzheimer’s). Data does not yet exist for such a study.
Why is there so much difference from one study to the next?
Studies of aspirin are not unusual in this regard. This is a great unanswered question, not just in epidemiology but all through the life sciences. Even after accounting for placebo effect and biases in perspective from one investigator to the next and differences among sample populations, there is a lot more disparity in outcomes than we can explain. That’s life.
My bottom line is that most people over 50 can benefit from daily aspirin or ibuprofen, as it lowers risk of cancer, dementia, and arthritis as well as heart disease and stroke. Diabetes patients might start a few years later. I would suggest that if you have stomach or bleeding issues with aspirin, you will know it, and stop taking it. If you have a family history of hemorrhagic stroke, don’t mess with aspirin at all.
Did you see this?
“Aspirin, take two: Research identifies a second effect of the drug against inflammation
Aspirin has a second effect, researchers have found: Not only does it kill cyclooxygenase, thus preventing production of the prostaglandins that cause inflammation and pain, it also prompts the enzyme to generate another compound that hastens the end of inflammation, returning the affected cells to homeostatic health.
Of course the problem with aspirin is bleeding, not just in the stomach, but bleeding in the brain which may be too small to be noticed, or also may be big and a life threatening stroke; and also bleeding in the retina which causes blind streaks across the field of vision. On the other hand, one can also have a stroke from a blood clot in the brain or in the retina. So the question is how to find a balance. Well, like Josh said, if you have a family history of bleeding, stay away from aspirin; but what to do if you are like me and have a family history of both bleeding and blood clots? In that case I would have to trust nature for a balance and stay away from aspirin.
This article suggests aspirin as a treatment and not just a preventive for breast cancer.
Aspirin Suppresses the Acquisition of Chemoresistance in Breast Cancer by Disrupting an NFκB–IL6 Signaling Axis Responsible for the Generation of Cancer Stem Cells
Our studies, using in vitro and in vivo tumor xenograft models, show a strong beneficial effect of ASA [aspirin] in the prevention of breast carcinogenesis. We find that ASA not only prevents breast tumor cell growth in vitro and tumor growth in nude mice xenograft model through the induction of apoptosis, but also significantly reduces the self-renewal capacity and growth of breast tumor-initiating cells (BTICs)/breast cancer stem cells (BCSCs) and delays the formation of a palpable tumor. Moreover, ASA regulates other pathophysiological events in breast carcinogenesis, such as reprogramming the mesenchymal to epithelial transition (MET) and delaying in vitro migration in BC cells. The tumor growth-inhibitory and reprogramming roles of ASA could be mediated through inhibition of TGF-β/SMAD4 signaling pathway that is associated with growth, motility, invasion, and metastasis in advanced BCs. Collectively, ASA has a therapeutic or preventive potential by attacking possible target such as TGF-β in breast carcinogenesis.