ASPIRIN IN HEART HEALTH: PART 1

Aspirin in secondary prevention, AFTER a cardiovascular event.

Aspirin is a household word. The chemical name of the compound is acetylsalicylic acid, which is referred to simply as ‘Aspirin’. Aspirin, registered in 1899, is the name of acetylsalicylic acid that was developed by the German pharmaceutical company Bayer in the late 1800s. The fascinating background to that is for over 2000 years prior to Bayer’s discovery, there was a realisation that something in the leaves of a willow tree could give therapeutic benefit for pain relief. In fact, a group of agents or salicylates in the primary compound were derived from the naturally occurring compounds within the leaves of the willow tree. 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 tablets of the formulation produced each year. Aspirin works by blocking a special enzyme called cyclooxygenase. This enzyme then alters production of other compounds or chemicals which act as chemical messengers, 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 IN THE BRAIN:

Prostaglandins within the brain, influence the way fevers develop. Therefore, if you are in bed with the flu and have a fever, by taking a couple of aspirin and blocking your cyclooxygenase, you will lower your prostaglandin production that is responsible for the fever, hence reducing your temperature.

PROSTAGLANDINS IN FEELING PAIN:

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 lowering your prostaglandin production, will ease the pain.

PROSTAGLANDINS IN INFLAMMATION AND SWELLING:

Prostaglandins also have an effect on the way blood vessels respond to 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.

PROSTAGLANDINS PROTECT THE LINING OF THE STOMACH FROM ACID:

Another effect of prostaglandins is help protect the lining of the stomach from acid. This is important to understand

because if you use aspirin for any length of time, it is quite possible to decrease the prostaglandins within the stomach which may lead to less resistance in stomach lining and the formation of an ulcer. This is where side effects from aspirin lead to possible bleeding within the gastrointestinal tract. It is the same process of cyclooxygenase being blocked, thus, reducing protective prostaglandins in this situation, which leads to increased risk of erosions or ulcers within the upper GI tract and therefore possible bleeding. This is one of the side effects that 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. Taking a couple of tablets on the rare occasion when we have a headache, a sore throat or even a flu with fever like symptoms, will not have detrimental effects on the gastric or upper gastrointestinal lining, however, aspirin will have an effect on reducing the impact of the prostaglandins.

Aspirin reduces the risk of subsequent heart attack.

PLATELETS AND THE EFFECT ON BLOOD CLOTTING:

However, there are reasons to take aspirin for the longer term. The role that aspirin has in reducing the stickiness of platelets is very important. 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. If there is a cut and foreign material or factors from the tissue come into contact with the platelets, the platelet activation leads to platelets clumping. 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 with aspirin, 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 showing benefit in terms of reducing the risk of subsequent heart attack. Importantly this collection of trials very specifically revealed very highrisk patients, i.e. 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, thus, stopping or reducing the risk of a second event. The following article, (Part 2), will discuss if taking aspirin before a person has a heart attack, i.e. primary prevention, has the same beneficial effect as in secondary prevention.