Aspirin or acetyl salicylic acid was first produced in 1897 by Dr. Felix Hoffman while he's working for Frederick Bayer and Company. 

So how does aspirin work? Aspirin is a Cox-1 inhibitor. Cox-1, an enzyme that is crucial to creating a potent glue called thromboxane A2 between platelets. Platelets are cell fragments that help form clots. With Cox-1, inhibited platelets do not stick together very well, and this prevents clot formation in blood vessels.

Keep in mind, by affecting the Cox-1 enzyme, aspirin also decreases a group of proteins called prostaglandins. Prostaglandins are responsible for protecting the lining of the GI tract. This is an important effect we will talk about later.

The story of aspirin in heart health began in 1988 when an article was published in the New England Journal of Medicine titled Final Report on the Aspirin Component of the Ongoing Physician's Health Study. The Physician's Health Study was a trial to determine whether 325 milligrams of aspirin every other day decreased cardiovascular mortality. This study showed there was a 44% reduction in the risk of a heart attack in the aspirin group versus placebo.

Interestingly, even though aspirin reduced the risk of heart attack, there was no decrease in mortality related to all cardiovascular causes. More importantly, the risk reduction with aspirin was only seen in those who were 50 years or older. Despite these limitations to aspirin's, benefits diffused with lit, medical providers and the general population held onto this belief that aspirin was a great tool to prevent heart attacks and strokes in everyone without really understanding who should be taking it and the consequences of taking a regular aspirin.

As time passed, our understanding of aspirin changed. Adaptable and other studies showed aspirin 325 milligrams had no more benefit than 81 milligrams in preventing cardiovascular events. This led to many people recommending a decrease in the dose of aspirin for prevention from 325 milligrams to 81 milligrams.

As our understanding of aspirin continued to evolve, physicians have further refined how aspirin should be used. In the beginning of 2022, the United States Preventive Services Task Force released a guideline clarifying who should and who should not take aspirin. Just before we get into this, it is important to understand how we assess cardiovascular risk.

Whether it is deciding to start a statin, which is a type of cholesterol medication, or whether you are recommending aspirin to prevent cardiovascular complications, you need to assess a person's cardiovascular risk. The American College of Cardiology and American Heart Association developed the Pooled Cohorts Equation, or PCE, to estimate the risk of a cardiovascular event like heart attack or stroke. You can access this estimator through the American College of Cardiology or through apps like MD calc.

To use this equation, you enter demographic, historical and clinical information into a formula, and it outputs the ten year risk of developing a cardiovascular event. Those with a less than 5% chance are low risk, five to 7.4% are borderline risk, 7.5 to 19.9% are intermediate risk, and 20% or more are high risk.

It is important to understand that age is the strongest risk factor that influences the risk estimation. So, who should take aspirin, and is there a point we should stop recommending it? To answer that, here are the four takeaways from the United States Preventive Service Task Force guidelines on aspirin use for prevention of cardiovascular events. Keep in mind the following does not apply to those who have already had a cardiovascular event, like heart attacks or strokes.

Number one aspirin does decrease the risk of heart attacks, also called myocardial infarctions, and ischemic strokes where blood supply is cut off to a portion of the brain. We must remember that low dose aspirin does provide a benefit in reducing heart attacks by 10% and ischemic strokes by 18%. However, despite this reduction and despite newer studies, aspirin was not shown to change cardiovascular mortality or all cause mortality, which is death for any reason.

So what is the major drawback of aspirin use? Well, that brings us to point number two. Number two aspirin does increase the risk of bleeding. Remember, aspirin decreases prostaglandin production, which normally protects the lining of the GI tract.

As a result, aspirin does increase the risk of major gastrointestinal bleeding by 57%. And that does not matter if you use high or low dose aspirin, which I was quite surprised to learn. In addition, high dose aspirin increases the risk of hemorrhagic stroke by 33%, while low dose aspirin showed no associated increase in hemorrhagic stroke.

The potential for bleeding is the reason for most people, the risks of using aspirin outweigh the benefits. However, those at high risk of cardiovascular events may see an overall benefit when compared to the risk of bleeding. As a result, the United States Preventative Service Task Force recommends considering aspirin to prevent cardiovascular events in those 40 to 59 years old with a 10% or greater ten year cardiovascular risk.

Number three, starting aspirin in ages 40 to 59 with a ten year cardiovascular risk of 10% or greater results in a gain of quality life years. But not so for older populations. A key measure of how a therapy benefits a population is called a quality adjusted life year or quality.

Qualities are an economic measure that is made up of a quality of life measure and a length of life measure. One year of perfect health is counted as one quality adjusted life year. Modeling data incorporates the risks and benefits of a therapy to help calculate the qualities that may be gained or lost by a therapy.

Starting aspirin in those ages 40 to 59 with at least a 10% cardiovascular risk resulted in a net gain in quality adjusted life years. As a result, Aspirin should be considered in this population. When studies looked at those aged 60 to 69 years old, the net benefit seen previously in younger groups began to decrease.

Studies in ages 60 to 69 show a slight benefit to slight harm for preventative aspirin, depending on the individual's cardiovascular disease risk. As we look at those in even older populations, we see only a net harm. For example, in 2018, the Asprey trial was published.

Asprey stands for aspirin in reducing events in the elderly. It looked at patients who were 65 years and older who did not have cardiovascular disease, dementia or disability. Participants were randomized to two arms those who were started on 100 milligrams of interic coated aspirin for cardiovascular disease prevention and those who started on placebo.

The study highlighted that those who received Aspirin had a significantly higher risk of death from any cause. Oddly, the higher risk of death in the aspirin group was associated with a higher risk of cancer related death when compared to the placebo group. Does this mean aspirin causes cancer? Absolutely not.

The important takeaway from the study is that all cause mortality was higher with aspirin use than placebo. The question as to why cancer related deaths were increased in the study needs to be further investigated. Another related point is that starting aspirin at 70 years old is not the same as continuing aspirin at 70 years old.

Keep in mind, someone who started aspirin at a younger age hopefully had an increased risk of cardiovascular disease. As we know, age is a strong risk factor for cardiovascular risk. With time, an individual's risk will likely worsen, and benefit may still be there for that person to continue aspirin beyond the age of 70 as long as their bleeding risk does not outweigh that benefit.

Number four recommending aspirin is dependent on balancing the benefit of reducing cardiovascular events and the risk of bleeding. In the end, the United States Preventive Service Task Force highlights the fact that we need to individualize a recommendation of aspirin for prevention of cardiovascular events. Aspirin provides an absolute benefit in preventing cardiovascular events of 2.5% in the same breath. Low dose aspirin is not as benign as we once thought, and we can have significant negative consequences, resulting in an absolute risk of increasing bleeding of 1%. What is clear is that we should no longer provide a blanket recommendation for all patients to take aspirin to prevent cardiovascular disease, but rather discuss risks and benefits of preventative aspirin use based on an individual's risk risk and consider discontinuation for those at low risk of heart attack or stroke.