Doctor Warrick
Aspirin is a household word. The chemical name of the compound is Acetylsalicylic Acid, a mouthful that we are happy to refer to simply as “Aspirin”. Aspirin interestingly is a registered name of Acetylsalicylic Acid that was developed by the German pharmaceutical company Bayer in the late 1800s, the name “Aspirin” being registered in 1899.
The fascinating background to that is for over 2000 years prior there was a realisation that something in the leaves of a willow tree could give therapeutic benefit and so in fact a group of agents or salicylates as the primary compound were worked on and derived from the naturally occurring compounds within the leaves of the willow tree, which had been noted to have health benefits for millennia.
Since the refining of Acetylsalicylic Acid and the marketing of Aspirin, its use has become widespread and currently is the most widely used medical preparation in the world with somewhere around 100 billion pills of the formulation produced each year. These are almost incomprehensible numbers but when you stop to think about what it can do, it starts to make a bit of sense.
Aspirin works by blocking a special enzyme called Cyclooxygenase, it is not important you remember that enzyme, however, it is useful for you to understand that that enzyme then alters production of other compounds or chemicals which act as chemical messengers. The chemical messengers produced by Cyclooxygenase are called Prostaglandins. These Prostaglandins occur throughout the body in different situations and altering their production has an impact in a range of different scenarios.
Prostaglandins within the brain influence the way fevers develop. Therefore if you are in bed with the flu and have a fever, taking a couple of Aspirin and blocking your Cyclooxygenase you will lower your Prostaglandins that are responsible for the fever, hence reducing your temperature.
Prostaglandins have a role in appreciation of pain and the way pain receptors respond, so that if you have a headache (perhaps with your fever) then blocking your Cyclooxygenase and altering your Prostaglandin production will ease the pain.
Prostaglandins also have an effect on the way blood vessels respond in settings of inflammation, so if you had a sore arthritic knee from too much work in the garden, the associated swelling could be reduced by again blocking the Cyclooxygenase which will reduce the Prostaglandins involved in the inflammatory response. So for pain, fever and inflammation it is pretty handy to keep a box of Aspirin in the cupboard to use on an as needed basis. I am sure we have taken relief from manipulating our Prostaglandins using a Cyclooxygenase blocking agent i.e. taking a couple of Aspirin and going to bed.
One of the other things that Prostaglandins do is help protect the lining of the stomach from acid. This is important to understand because if you start to use your Aspirin for any length of time it is quite possible the change in the Prostaglandins within the stomach may lead to less resistance to the formation of an ulcer. This is where we can run into problems with side effects from Aspirin leading to possible bleeding within the gastrointestinal tract. It is the same process of Cyclooxygenase blocking, reducing protective Prostaglandins in this situation, which leads to increased risk of erosions or ulcers within the upper GI tract and therefore possible bleeding. Let’s keep this in mind because this is one of the side effects we really need to be aware of when we are considering the risks and benefits in terms of taking Aspirin, particularly for the longer term. A couple of tablets on the rare occasion when we have a headache or a sore throat or even a flu with fever like symptoms, will not have detrimental effects on the gastric or upper gastrointestinal lining, however, ongoing continued impact on the Prostaglandins will.
There are, however, reasons we may wish to take Aspirin for the longer term. The area that I would like to focus on for the remainder of this article is the role that Aspirin has in reducing the stickiness of platelets. Platelets are the small particles in the blood stream involved in the formation of clots. These small particles become activated when there is any irregularity within the blood vessel. For example if there is a cut and a foreign material or factors from the tissue come into contact with the platelets, the platelet activation leads to platelets clumping and if platelets clump and they happen to be in an artery then the clot that is subsequently formed can block that artery. A ruptured plaque within an artery is the mechanism by which a heart attack occurs when that ruptured plaque exposes tissue factors to the platelets that lead to them clumping and forming a clot. The benefit of reduction of platelet stickiness in reducing the risk of a heart attack has been demonstrated multiple times since 1988.
So 30 odd years ago, a trial called the ISIS-2 trial showed that giving Aspirin to patients very early on after a heart attack would reduce the likelihood of that patient having a heart attack in the future compared to not giving Aspirin at all. This first trial demonstrating benefit of Aspirin was followed up by many others, all of them in the setting of preventing a second event and all of them showing benefit in terms of reducing risk of subsequent heart attack.
Importantly this collection of trials very specifically sort out very high risk patients, that is individuals who have demonstrated themselves at being very high risk by having a heart attack and treating that group only. The ISIS-2 trial and subsequent trials that followed supported the use of Aspirin in secondary prevention i.e. in stopping or reducing the risk of a second event.
Where controversy has simmered over subsequent years is whether giving Aspirin to people BEFORE they have an event (we call this primary prevention) i.e. before they have declared themselves as very high risk offers any benefit. In the last three to six months a number of trials have come out to try and answer this question. In August a study called ASCEND was published in the New England Journal of Medicine. This was a trial that studied patients who were diabetic, but had not had any history of heart problems; they were a primary prevention population. These patients, 15000 of them were in fact followed for over seven years and although at the end of that time there was some suggestion that the risk of having a heart attack was reduced in the Aspirin group, this benefit was offset by an increased risk of bleeding caused by being on long term Aspirin and the impact that had on the risk of bleeding from the upper part of the gut or the risk of bleeding into the brain. Unfortunately the ASCEND trial did not show benefit in giving Aspirin for a group of diabetic patients who had not had previous heart problems.
Released at the same time as the ASCEND trial results but in a different publication, The Lancet, a study called ARRIVE showed that Aspirin had no significant benefit in outcome when given to 13000 subjects randomised to Aspirin or not, these people were people with moderate cardiovascular risk but had not had a previous heart attack or stroke. (In doctor speak moderate risk means between 10 and 20% risk of an event in 10 years) This group of patients was followed for approximately six years and during that time any benefits in reduction of stroke or heart attack were matched by complications of bleeding.
The most recent of the Aspirin in primary prevention trials was the ASPREE trial. This enrolled nearly 20000 people across the world to try and evaluate whether Aspirin given to otherwise healthy older adults, over 70 years of age, would improve function and reduce death. These participants in the trial were followed for approximately six years and there was no suggestion that giving Aspirin to this healthy group of older citizens made any difference, in fact there was even a small suggestion that it could worsen outcome. It is worth noting that these healthy older adults had got to be healthy older adults because they hadn’t had coronary artery or cardiovascular disease up until that point and so to some degree had been self selected as a relatively low risk group to benefit from Aspirin in the context of reducing cardiovascular risk.
So where does all this information leave us now? It would certainly seem that Aspirin shouldn’t be in the water just to try and reduce risk of heart attack and stroke for everyone. It certainly doesn’t have a clear-cut indication in normal primary preventative situations of low or moderate/intermediate risk patients. There is some data to suggest that patients with elevated blood pressure may well benefit from being on Aspirin, that is probably because elevated blood pressure can push people into a higher risk category.
In my own practice, I tend to try and be more precise about how to evaluate risk that an individual may be carrying in the primary preventative setting by undertaking imaging of their coronary arteries. None of the primary prevention studies above incorporated imaging as a selector for Aspirin therapy or not, so the use of imaging in primary prevention and Aspirin remains somewhat unanswered and speculative. My feeling, however, though is if we find people with high or very high risk features on imaging then understanding the pros and cons of Aspirin based on the individual’s situation that it may well be a reasonable consideration. This is something that needs to be considered on a patient to patient basis with all the information available and with a clear conversation between doctor and patient striving for the best management strategy for that individual. I have written a book on this very subject.
When it comes to secondary prevention i.e. people who have had a heart attack or stroke, there remains no question that Aspirin is beneficial and these current trials do not impact or alter the way we view Aspirin in that situation.
This means that if you have had a problem with your heart arteries or neck arteries or arteries in the legs and you have been put on Aspirin by your doctor that Aspirin is going to be doing a good job for you. PLEASE DO NOT STOP YOUR THERAPY BASED ON THE WAY SOME MEDIA OUTLETS HAVE PRESENTED THE DATA FROM ASCEND, ARRIVE AND ASPREE, CHECK IF HOW IT RELATES TO YOU.
At the end of the day, every treatment needs to be considered for the individual patient based on the merits of benefit of that therapy weighed up clearly against the risks that could be inherent. This is something that your doctor needs to work through with you and something you need to be aware of and informed of.
Please work with your doctor for your own best outcomes.
Wishing you the very best of health.
