Aspirin Foundation Meeting 2013

History of aspirin use against cancer

Prof Peter Elwood - University of Cardiff, UK

I directed an MRC unit and while directing that unit we set up the very first randomised trial of aspirin and heart disease. But my interest has continued since then and I think the developments on cancer now are just of incredible interest and incredible value to the community. I feel tremendously privileged to be here, having been in on aspirin and heart disease right at the beginning. There have been numerous conferences, both here and abroad, and I have travelled the world on the back of aspirin talking about the benefits in vascular disease. Now, of course, it has opened up with benefits in cancer.

But my talk this morning, I’m giving two talks, the first talk is on the history of aspirin and I’m dealing with the transition, as it were, when aspirin was originally for headaches and for control of fever and then it broke into the news with evidence on a reduction in heart attacks. We were involved in that very early stage and there was a lot of work going on. Really the history of aspirin follows on the history of platelets. Platelets were first described about 1740 by a French physiologist who described platelets but he said they looked like globules of lymph. He thought that they coalesced into white cells. But then Osler, William Osler, gave a beautiful description about 1874. He gave a beautiful description of platelets with pseudopodia and he said these take part in thrombosis. That was a remarkable insight into the platelets. Further work was done on platelets and then around the early ‘60s Michael Davis in London showed that atherosclerosis, the hard plaques of atherosclerosis, could crack and platelets would immediately adhere to the crack in the platelet and platelets would grow and grow and then eventually block the vessel. So that was a great insight into heart attacks. So pharmacologists then started to look at things that would affect platelets and make them less active. We linked up with John O’Brien, he became a very great friend of mine, and John O’Brien called for a trial of aspirin in the reduction of cardiovascular mortality. In the late ‘60s we set up a trial. We admitted just about 1,400 patients who had had a recent infarct, we admitted them to a randomised trial using one tablet of aspirin a day and a placebo, of course and we showed a 25% reduction. Now that was an incredible success because in those days there was almost nothing could be done for heart attack. Bed rest was recommended, a fortnight in hospital in bed, of course that was later shown to be harmful and to increase the risk of a further thrombosis but aspirin really hit the headlines. Beta-blockers came out at the same time but the first beta-blocker, practolol, had to be withdrawn because of side effects. And beta-blockers then came on and play a very valuable part. But we had a tremendous thrill in that first trial. Within a few years there were six major trials, none of which were statistically significant. But Richard Peto, Sir Richard Peto, did a marvellous service by putting those six trials together in an overview, one of the first overviews, and he showed that together they were overwhelmingly significant. That really brought aspirin to the attention of practising physicians. Then Peto and Baigent and others set up ISIS-2 which gave huge numbers and gave a very thorough test so aspirin took off.

But then the recent development has been, I think, even more exciting where Peter Rothwell had the brilliant idea, the inspired idea, of going back to those early aspirin trials and following up the subjects for up to twenty years and showing that there was a reduction in cancer. Now there were hints gathering and we reviewed the evidence from a number of sources. There were hints that aspirin might reduce cancer and might reduce metastasis, the spread of cancer, but Peter Rothwell put it together and reported on these long-term trials in which patients had been randomised to aspirin. He showed a remarkable reduction in aspirin.

So the whole thing has taken off but it goes back to platelets again because one of the effects of aspirin is to reduce the metastases, the spread of cancer. It is thought that it is the action of aspirin on platelets which reduces the ability of the platelets to carry, to seed, the cancer in distant parts and cause metastatic growths. So it’s a wonderful rounded story.

My second talk I’m privileged to talk about aspirin in the future. I’m not a prophet, I’m not going to talk about new uses of aspirin which might be discovered. No, I’ve just focussed on the next five or ten years, wondering how aspirin will come into common use in the community and frequent use by colleagues in clinical practice. I think there are two developments that will lead to that. One is a better presentation of the risks and benefits of aspirin. Everyone has apprehension about aspirin because it causes bleeds, but let’s get that into perspective. There’s a very small risk of a bleed; there is no evidence in the literature that those bleeds are ever fatal whereas the conditions that aspirin reduces, that aspirin prevents, are fatal conditions. So the balance in terms of a serious outcome is very different. There are a number of risks and benefits that have to be presented with aspirin on heart disease and on cancer. I think we’ve got to get a new way of presenting that and I’m going to present in my talk a visual way of presenting the risks of a heart attack, of stroke, of cancer, a visual presentation of the reduction by aspirin and in the background the risk of a bleed. I think that is going to make it understandable by the man in the street where giving a few percentage reductions just confuses.

The other way in which I think aspirin is going to come into common use is alongside colorectal cancer screening. Colorectal screening has been introduced in this country and everybody between the age, I think it’s 60 to 75, is offered screening by a faecal test for blood in the faeces and if that’s positive then by colonoscopy. Many people refuse the screening test, it’s rather unpleasant having a long bit of hosepipe shoved up the bottom and 50% of people refuse. I think those 50% should be told there is an alternative, a small dose of aspirin a day has a reduction in colon cancer which is equivalent and, in fact if you look at it in detail, it is greater than the reduction from colorectal screening. The other aspect of colorectal screening is a small proportion of those who have blood in their faeces and are therefore at a very high risk of cancer, 6% of those people refuse to have the colonoscopy. I think there’s an ethical imperative that those people should be told there is an alternative – start taking aspirin.

So I think aspirin will come into general thinking and general use, probably alongside screening. Taken together they are much more effective, much more cost effective, than either on its own and I think that’s how it’s going to get into general clinical use. Then it will gradually be used in other cancers and the evidence is hardening, the evidence is accumulating, on cancers other than the colon.