Aspirin in the 21st century

Mechanisms behind bleeding with aspirin

Prof Angel Lanas – University Hospital Zaragoza, Zaragoza, Spain

What was the topic of your talk here at the meeting?

The main topic of my talk in this meeting has been on the mechanisms of bleeding. Because the bleeding adverse events of using aspirin is located in the GI tract, I focussed on the mechanisms of bleeding essentially in the GI tract.

How much of a risk is bleeding in the GI tract with aspirin?

It’s very well known that aspirin, even low dose aspirin such as 75mg or 100mg per day, is associated with an increased risk of bleeding. The actual risk is very small but because there are hundreds of thousands of people, millions of people, that are taking low dose aspirin around the world obviously we are just dealing with an important number of patients developing an upper or lower gastrointestinal bleeding.

Are some patients more prone to bleeding than others?

Today it’s clear that not everyone taking aspirin has the same risk. Only a very few number of people develop GI bleeding. In fact, we understand that only about… aspirin induces three extra bleeds per 10,000 patients per year so it’s not very much. So the real issue here is who is at risk of developing GI bleeding. Today we have some clinical factors. We know that the elderly and those who have a previous ulcer history are at the highest risk of developing a GI bleeding but we also know that it may be some genetic background in these patients. So we are doing research in trying to uncover which genetic factors are behind this risk.

Do you have any advice on how to use aspirin to try to avoid bleeding complications?

Anyone being prescribed with low dose aspirin should be screened for potential risk factors. So anyone having some of these risk factors, as I mentioned before, age older than 70, a previous ulcer history, should receive prevention therapy. We have very good prevention therapy today so these patients at risk should receive a gastroprotective agent such as a proton pump inhibitor. Probably we also believe that if they have an H. pylori infection, Helicobacter pylori infection, probably it’s a good way to prevent problems by eradicating the infection.

Can you tell us about the work you have also been doing in CRC?

Today it’s very clear that aspirin can prevent colorectal cancer so the real issue here is, first of all to develop clear guidelines for those patients who should benefit by receiving aspirin. Then, in this situation I think that we have different factors to be balanced. First of all, we need to put in the benefits those patients who need aspirin because of the prevention of cardiovascular events. Then the benefits for those who are receiving aspirin should have a reduction in the risk of colorectal cancer. On the other hand, we should just put on the balance those risks for developing bleeding. So then it’s very important to describe who is the population that will benefit with aspirin the most. That’s part of the research ongoing today and we are also trying to understand that population.

Has anyone developed an algorithm to help determine who might benefit from chemoprevention with aspirin?

We still are a little bit far from that, not very far, but we believe that probably the population over the age of 50 are those who may benefit, especially if they have a colorectal cancer family history, they may benefit with aspirin treatment. Because especially if they have also a risk factor for cardiovascular events so they may benefit from having a reduction in the colorectal cancer risk, a reduction in the cardiovascular risk at the cost of a minimal risk of having a bleeding event. But also I think it’s important to understand the different weight of the events. So, probably it’s not the same to have a bleeding event as a myocardial infarction. So the impact on the quality of life may be very different and if it’s different we need to work on these particular issues.

Is there any guidance on the dose of aspirin that should be used for CRC chemoprevention?

To me it’s very clear that the only potential use for aspirin in this particular balance and risk should be around 100mg. Anything going beyond 300mg, I think that this is going to be difficult to accept in terms of risks and benefits.

Do you have anything further you would like to add?

I’ve been also working in collaboration with Paola Patrignani and Carlo Patrono in understanding the mechanisms of aspirin in the prevention of colorectal cancer. We believe that one of the main effects in prevention of cancer depends on the inhibitory action of platelets with aspirin but our recent studies suggest that also aspirin is able to acetylate for up to 24 hours the COX enzyme in colorectal cancer cells and in colonic cells. I think that this is an important issue in our way to understanding the mechanisms in the way that aspirin prevents cancer.