Aspirin in the 21st century
Aspirin for cancer treatment and prevention
Prof Peter Elwood – Cardiff University, Cardiff, UK
One of the early studies, one of the first studies, I set up was an aspirin trial, a randomised controlled trial of aspirin in the reduction of cardiovascular mortality. That was the first randomised trial that was published; it brought aspirin to the attention of many other workers and really started the modern phase of interest in aspirin which is just expanding all the time. We’ve had a wonderful meeting today just reviewing aspirin. But for me, as an epidemiologist, I’m interested in the population effects of aspirin and the effects of the diseases to which it is relevant – vascular disease, cancer. Many of the people here are interested in the mechanisms and we need each other. We need to know how effective it is in the population but we also need to know how it works, perhaps how it can be enhanced further, perhaps other further uses of the aspirin can be found.
I felt today, I quoted to the audience, I quoted the saying of Keats. Keats said that science is like unravelling the rainbow and he meant it in a disparaging way, that if you know that a rainbow is just an inevitable consequence of refraction and reflection it takes the mystery out of the rainbow. I think he was totally wrong and today we have seen a summary of the effects of aspirin in the community and individual patients, both in prevention but now treatment of cancer is a hot topic. But we’ve also been looking at the mechanisms of action and the rainbow, if we can call aspirin the rainbow amongst drugs, it has been gilded by the work that’s going on on its mechanisms.
What was the first piece of evidence hinting that aspirin may be more than just a painkiller?
Strangely, the very first data that I came across was an effect of aspirin on metastatic spread of cancer in mice. I went to Archie Cochrane and I said, ‘Look, there is background literature on two effects of aspirin, one in cancer and one on vascular disease through an effect on platelets and an effect on platelets in thrombosis.’ I said, ‘Shall we pick up one of those and set up a study?’ And he immediately said, ‘Well, we wouldn’t have resources to do cancer, let’s settle for heart disease.’ And the heart disease study really hit the headlines because we showed a 24% reduction in mortality in subjects with past myocardial infarction and that started it all.
So is aspirin the cure-all drug of the future?
I see a dilemma in relation to the future. My other area of work, main area of work, is in healthy living, healthy lifestyles, and there are tremendous benefits from following a healthy lifestyle. There are benefits in diabetes, a huge reduction in diabetes, from a healthy lifestyle, reductions in vascular disease, in cancer and in dementia; reductions of 30-70% in those diseases. So I wrote a little booklet and the title of the booklet was Better Than Any Pill, better even than aspirin, better than any pill, and no side effects. The side effects, in fact, are all pleasurable and beneficial. So I think we’re in a dilemma – it’s very difficult to persuade people in the community and even patients to adopt a more healthy lifestyle. The benefits are enormous but there’s reluctance. We’re all indulgent, we don’t want to spend time exercising, we don’t want to be too choosy in our diet, we just want to eat what we like. We’re all indulgent and we’re all getting a bit fatter over the years and that’s spreading through the community. Aspirin, I think, I fear that aspirin may be seen by some people as a substitute. As was said this morning, some people will see aspirin as a healthy lifestyle and so instead of attending to their activity level, their diet, their alcohol intake, their smoking, they’ll just say, ‘Oh, but I’m on aspirin. Aspirin will protect me from the diseases which account for 70% of mortality and morbidity in the community.’ So I urge that aspirin is always recommended within the context of healthy living. But I go further, I think there’s a very marked difference between the treatment of disease and the prevention of disease. The treatment of disease has been delegated to healthcare professionals and we are all trained, intensely trained, in the treatment of disease. The prevention of disease and the preservation of health is your responsibility, the responsibility of the man in the street. So I think rather than saying that doctors should discuss when aspirin should be recommended, what restrictions should be put on aspirin, I think we have a responsibility to give the evidence to the man in the street, to every patient, and say, ‘Now, there are the benefits, there are the risks, that’s for your to decide but first of all improve your lifestyle and then think of aspirin as an added benefit.’
Why is looking at the mechanism of action of aspirin in detail important?
I think for conviction; there’s always doubt from observational evidence. If people on aspirin happen to have less heart disease is it because people who take aspirin happen to take more exercise. The only way of answering that kind of question is from a randomised trial. These trials are difficult, they require intense co-operation by patients or by subjects and we need large numbers. I think it’s essential. We don’t want just anecdotal evidence. Medicine thrived for years on anecdotal evidence, now we want evidence based medicine and that requires a fairly detailed knowledge of mechanisms.
Can you tell me about the work you have done looking at the treatment rather than prevention of cancer using aspirin?
The focus has been on the prevention of cancer but there are actually at least 38 studies in the literature in which, they’re observational studies, only a very few are randomised trials and they’re very, very small randomised controlled trials, but there is evidence, growing evidence, that aspirin which is taken by people who have had a cancer diagnosed, that they have a better survival and a lower incidence of metastatic spread of the cancer. Now, that is observational evidence but it comes from a large number of studies, chiefly in colorectal cancer, in breast cancer and in prostate cancer and in very few other cancers. So it’s very important that that is looked at in terms of randomised trials and mechanisms. It’s found that when looking at mechanisms there are one or two markers in terms of enzymes or genetic mutations which indicate whether aspirin will have a major effect or little or no effect. Now, that is very difficult to tease out but a lot of work is going on in that and it looks as if the small proportion of people who have a particular mutation, we call it PIK3CA, have a massive benefit from aspirin, there’s a bit of doubt about others. There is sufficient evidence to say they should not be denied aspirin and, after all, there are the cardiovascular benefits from aspirin at the same time. But that shows the need both for epidemiological studies, randomised controlled trials, and for in depth studies of mechanisms.
What about the future use of aspirin? Can you see profiling patients to see who could benefit the most?
My own view is that the public have a right to know about every measure which will preserve their health and reduce their disease. So I think one of the most important things is that bodies like task forces in America, like NICE in the UK, do not sit in judgement but that they recommend that the evidence is given to the man in the street, to every patient. The evidence is given and the person is urged to make their own choice. There’s such a profound difference between treatment where we have a responsibility delegated to us as medical practitioners and prevention, which is every man’s business. I think it’s a very important distinction which I fear is not recognised by these task forces and by NICE and other similar bodies.
