Islon Woolf MD
Sep 24, 20184 min
Aspirin is a natural medicine. It is an extract from White Willow bark and its use dates back 2500 years to Hippocrates. One of its mechanisms of action is an anti-platelet agent - it stops blood from clotting. Caused in part by blood clots, heart attacks can be prevented by Aspirin. However, stopping the clotting of blood comes at a cost; a side effect is major bleeding into the brain and the gastrointestinal tract. Can aspirin prevent heart attacks without causing too many side effects?
Before we move on, it is important to understand the difference between primary and secondary prevention. Primary prevention is preventing an event in a low risk patient - a healthy patient that has not yet had an event. Secondary prevention is preventing another event in a high risk patient - a patient that already had an event. Most medications are first studied for use in secondary prevention. After all, the high risk group has the most to gain and the least to lose. A patient that already survived one heart attack, for instance, is at high risk of dying from another in the near future. A medicine that can prevent another heart attack, even if it has side effects, is acceptable.
One of our biggest mistakes is to use a medicine for primary prevention based on its success in secondary prevention. This extrapolation usually fails because a different benefit to harm ratio emerges. There is less benefit in a low risk patient but the potential for harm (side effects) is the same. An excellent example is the osteoporosis medication Fosamax. It prevented new fractures in high risk women with a prior fracture; however, when we started using it in younger women with only slightly thinning bones we started to see side effects. The side effects were rare, but when tens of millions of healthy patients are taking a drug, the rare becomes significant.
Aspirin definitely works for the secondary prevention of heart attacks. Does it work in primary prevention? This is a little more controversial. Primary prevention patients don’t get much benefit out of Aspirin, yet still get the harms (bleeding events). Recently, an article was published in the New England Journal of medicine that received much media attention.
It showed that Aspirin does more harm than good for the primary prevention of heart disease in the elderly.
The study had an excellent design. It was a randomized placebo controlled clinical trial. The trial recruited 19,114 patients, 70 years or older, with no history of heart problems or aspirin use. They were randomly assigned to take aspirin 100mg a day versus a placebo and followed for 5 years. The trial was funded by Bayer but certainly lacked bias; it yielded negative findings for them.
Over 5 years there was no difference in heart attacks or death from heart attacks. Notice no separation of the Aspirin and placebo curves (see below):

There was, on the other hand, a difference in major bleeding. Over the 5 years, the Aspirin group had a 38% relative increase over placebo (see below). Keep in mind that the absolute incidence of these bleeding events was rare: about 1 in 500 patients. However, if you are getting nothing out of a drug, a 1 in 500 major bleed rate is unacceptable.
This is certainly a blow for the use of aspirin in the primary prevention of heart disease. Although Hippocrates was first to use Aspirin, we may be forced to invoke his ethics instead - “First, do no harm”.
Yet, prior studies have yielded mixed results. Some showing the benefits outweigh the risk and others that do not. To make things more confusing, the line between primary prevention and secondary prevention is blurry. It is more of a spectrum. There are many factors that contribute to assess someone’s risk of heart disease. What can be said, for instance, of a patient that has a very high plaque score on CT scan but never had a heart attack? Is that primary prevention?
Ultimately the choice should be made on a case-by-case basis. A process of shared-decision making.
Whenever I point out to a patient that there is no evidence their supplement works, many justify their use with a sort of Pascal’s wager for supplements. “If it works, I can live better and longer. If it does not, what’s the harm?” Unfortunately, physiology doesn’t work that way. If it is strong enough to work, it is strong enough to harm. The body has thousands of interconnected pathways all in balance. A push of one system results in a cascade of effects - some good, some bad. As in the case of Aspirin, turning off clotting is both good and bad. It is a war between benefits and harms.
Aspirin is by far the most promising and best studied “natural” medicine of all time. Yet, in a healthy patient the benefits are negligible; making the rare harms unacceptable. Other supplements are less promising and less studied. Thus, the real supplement wager is: what is the likelihood a supplement is benefiting a healthy person? What is the likelihood it harbors side effects? Do the benefits outweigh the harms? In a healthy person, probably not.
#supplements #aspirin #clinicaltrial #antagonisticpleiotropy #whitewillowbark