The potential of aspirin in the prevention and treatment of cancer

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Published: 17 May 2017
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Dr Gareth Morgan - Cardiff University, Cardiff, UK

Dr Morgan speaks with ecancer at the 1st Cancer Research @ Bath Symposium about repurposed aspirin in cancer prevention, and its synergy in bowel cancer screening.

He introduces the role of dietary salicylates, which aspirin matches, and cautions against overestimating the risks of regular aspirin use; while bleed risks are higher, risk of death reduces.

Dr Morgan notes the exception of bleeding in the brain, a significant risk to patients with high blood pressure, and considers how patients may reach a fully informed treatment choice.

Today I’m going to be talking about aspirin in the prevention and treatment of cancer and the potential that it has. Now aspirin is a very familiar medicine to lots of people, very useful in the treatment of vascular disease, in heart attacks and in strokes. One of the side effects with aspirin, of course, is bleeding so, I will be looking at the evidence on bleeding and showing some evidence that actually, it’s a rather safe medicine and potentially the undesirable effects of aspirin have been mis-estimated previously. So, then I’ll go on to talk about aspirin and prevention of cancer and in particular the evidence around bowel cancer and the practical application that aspirin may have as part of bowel cancer screening, where it could enhance and compliment existing screening techniques. Then I’ll go on to talk a little bit about aspirin and cancer treatment and the emerging evidence and the ethics of that situation which is difficult because we don’t have firm conclusive evidence on aspirin and cancer treatment. We’ve got trials on-going but there is suggestive evidence and the whole dilemma now is what do we do while we wait for the trials? Do we give cancer patients the information so they can decide or do we just wait for the trials to give us the reports? So, it’s a bit of an ethical situation. Then I’ll round my talk off by talking about the public health aspects of aspirin, how it could be potentially used to enhance aging. As we age our risk of vascular disease increases, our risk of cancer increases. So, could we potentially take an aspirin on age grounds, starting over the age of 50 – a public health consideration.

Which pathways are aspirin affecting?

Yes, with bowel cancer potentially that might be induced by programmed cell death, a process called apoptosis. Now it is very interesting because aspirin is acetylsalicylate and salicylate is found in nature in fruits and vegetable. So, we eat salicylate or a form of natural aspirin through our diet. And we know that in plants, in fruits and vegetables, that salicylate is part of the defence. It causes diseased or injured cells to die, a programme called apoptosis. So, it has that role in nature. So, we can open up the idea that as humans, when we eat salicylate through our diet, it could be causing the same process. We’ve evolved, if you like, to be gaining the benefits of dietary salicylate through our fruits and vegetables and that it may be causing cancer cells to die. So, an important, if not exclusive, mechanism could be programmed cell death or apoptosis in the cancer cells.

How are the side effects of aspirin overstated?

It’s very interesting because often people who take aspirin are also taking other medicines as well. They may be taking other blood thinners, if they are doing it for heart disease, or they may be taking other anti-inflammatory medicines if they have an inflammatory condition. So often the reports that we’ll get out is an estimate of combined effect of medicines when it’s in the community. Or if people turn up to say the accident and emergency department and they have bleeding, vomiting blood the first question might be, are you taking an aspirin? Therefore, it’s aspirin that’s suspected as the culprit for this. So, we’ve gone back to the trials, the original trial data in vascular disease, and looked at the bleeding outcomes of patients taking the aspirin. So, it’s very experimental evidence rather than the mixed and often biased evidence that you see in observational studies. And with that particular evidence we find, yes, there’s a 50% increase risk of aspirin, no dispute, no debate, aspirin increases the risk of bleeding in the stomach. But the risk of dying halves, which is very interesting. It almost is suggestive that aspirin is triggering more events but they’re less serious. Now within the community bleeds can occur spontaneously. Everybody’s at risk of a bleed whether they take an aspirin or not and aspirin is certainly enhancing that risk. But if that bleed, let’s say it was due to an underlying stomach ulcer, was to carry on, remain silent and then turn into a bleed, potentially that could be more serious if it occurs later, more difficult to treat, more likely to die. So, we’ve got this duel effect of aspirin from the trials where the number of bleeds increases by about 50% but the severity or the risk of dying falls by a similar amount. And when you combine the effect on frequency and severity, it comes out about equivocal; in fact, suggestive evidence that it may be even lowering risk of dying from a bleed. But the confidence intervals overlap one so we can’t say that conclusively but suggestive. So, we’ve got an interesting duel effect from aspirin. The interesting caveat to that, and the more difficult issue, is aspirin and bleeding in the brain. Now there is an increased risk of aspirin causing bleeding in the brain, a haemorrhagic stroke. Aspirin lowers the risk of an ischemic stroke which is due to a clot but due to a haemorrhagic stroke aspirin can potentially increase the risk. The biggest risk factor for a bleed in the brain is high blood pressure and so what may be happening in the community is there will be people with undiagnosed, untreated high blood pressure, taking an aspirin and the aspirin could precipitate or bring forward a bleed, if you like, a haemorrhagic stroke. So we can measure an increased risk of haemorrhagic stroke in the community. The one trial that’s interesting is the HOT trial, the Hypertension Optimum Treatment trial, which actually treated patients with the underlying hypertension and they were on aspirin and there were no excessive brain bleeds. So is aspirin causing bleeds in the brain, potentially yes. But what is the increased risk, that’s more difficult and if we were to adequately treat high blood pressure we may see fewer or less bleeds in the brain from aspirin. And it is a rare side effect - about one in five thousand to ten thousand people per year taking the aspirin.

Could you tell me more about the ethical complications?

Yes, basically with aspirin there are certain situations where you would encourage aspirin use. If somebody has had a heart attack, you’d almost suggest that aspirin would be mandatory to help prevent subsequent events. Where it gets very difficult is in the role of aspirin in healthy aging. Now, first and foremost, healthy aging is often about lifestyle. It’s about good exercise, diet, alcohol intake, smoking. And so, aspirin is part of that. There are a number of healthy behaviours and could aspirin be part of that healthy behaviour? So, first and foremost, we’re not advocating the aspirin instead of good lifestyle to reduce the risk. But the ethical dilemma comes if we were to suggest aspirin taking on age grounds. Now as we age the risk of vascular events, the risk of cancer increases and we think aspirin could be beneficial against both of those, stacked against the increase risk of a bleed, so it’s a benefit/risk trade off. Now who should make that decision, should it be a doctor that makes that decision or should it be the person themselves? We’ve got evidence from a citizen’s jury in Wales, where we ask members of the public exactly that question. That will be part of my talk today but what they said was we should have the evidence even when there is disagreement amongst doctors, so it is a debateable issue about whether you should take aspirin on age grounds to prevent illness. It is debatable and there are arguments and counter arguments against that. But the public that we spoke to in Wales, which we’ll present today, actually said, let us have the evidence and let us make the decision, even before there is agreement.