The headlines this week—aside from the hurricane, the typhoon, and the charge of sexual misconduct in the Supreme Court nominee—are all about aspirin. For older people, unless you live in the Carolinas or Hong Kong, this is definitely the story. A new study (reported as 3 separate studies but really just one study with three different endpoints) threatens to unseat aspirin from its coveted spot as the little-pill-that-could.
A single aspirin a day, many people believed, could stave off heart disease, stroke, cancer, and perhaps dementia. If taken as a “baby aspirin,” a dose of 81 mg a day instead of the 325 mg in a regular aspirin tablet, and with a special “enteric” coating to protect the lining of the stomach, it was touted as effective with virtually no side effects. The truth, unfortunately, seems to be that it is neither effective nor devoid of side effects when taken by healthy older people.
The study, published online in the New England Journal of Medicine, examines three plausible possible benefits of low dose, enteric-coated aspirin. First, they ask whether aspirin has a desirable effect on cardiovascular events such as heart failure requiring hospitalization, stroke, or heart attack. They found no difference in benefit between healthy older people in the US or Australia (where older was defined as over 70 except in blacks and Hispanics, where it was defined as over 65) who took 100 mg of aspirin and those who did not.
Next, they looked at whether aspirin has an effect on how long healthy older people live without developing a disability. Again, they found no statistically significant difference between those who took aspirin and those who didn’t.
Finally, they examined overall mortality in the aspirin-takers and the non-aspirin takers. Once again, the two groups were indistinguishable.
There was, however, one striking difference in outcomes between the 9525 people who were randomized to take aspirin and the 9589 people who were randomized to placebo: the risk of bleeding was significantly higher. And by bleeding, the investigators meant major bleeding such as a gastrointestinal bleed or an intracranial hemorrhage.
Not only did this randomized controlled study fail to show any benefit from taking aspirin, and not only did it show an increased risk of harm, but even when the results were subjected to subgroup analysis, no group emerged as potential beneficiaries. The authors looked at the composite endpoint (dementia, death, or persistent disability) in several pre-specified subgroups. One was gender: in the past, aspirin has been touted as preventive for healthy men but not women; in this study, neither men nor women benefited. Another was frailty (though I’m not quite sure how 421 of the “healthy” elderly subjects could have met the definition of frailty): in this study, neither the frail nor the non-frail benefited. If anything, there was a trend towards worse outcomes in the frail group, though the numbers were so small that the difference was not statistically significant and might well be due to chance.
No study is perfect and this one is no exception. The median period of observation was 4.7 years, a relatively short period with respect to the time needed to develop dementia or heart disease. The analysis was done on an “intention to treat” basis, which is the way such studies are supposed to be analyzed, but in fact only 2/3 of the people assigned to take aspirin were actually taking it by the end of the study period. The benefit of aspirin might therefore have been under-estimated. The risk of bleeding, however, which was already substantial in the aspirin users, may have also been under-estimated. For some reason, the study used a 100 mg dose even though a standard baby aspirin contains only 81 mg: maybe the results would have been different with an even smaller dose. But the strengths of the study are impressive. It was randomized; follow up was almost complete; data collection seems to have been thorough and careful.
I have a confession to make: for several years, I took a baby aspirin every day. I’m under 70 and I’m female, so my physician did not recommend that I take aspirin. I took it nonetheless because I really don’t want to have a stroke and thought that just maybe taking aspirin was something I could do to help. I took it because years ago, before I went to medical school, I worked in a hematology research lab and spent my days studying platelet aggregation. It turned out that people who had taken a single aspirin tablet within two weeks of my testing their blood showed markedly decreased clumping of platelets, blood cells that are critically involved in the clotting process. About a year ago, I had several episodes of subconjunctival hemorrhage, a benign form of bleeding involving the blood vessels of the eye. I worried the bleeding might be related to aspirin, so I stopped taking it.
Today, the evidence is compelling that for people without heart disease or dementia or stroke, an aspirin is more likely to cause harm than good. As of now, aspirin has joined the ranks of other failed panaceas such as estrogen and calcium supplements.