Aspirin in the 21st century

Conference overview: Aspirin in the 21st Century

Prof Peter Rothwell – The University of Oxford, Oxford, UK

The International Aspirin Foundation was set up in 1974 so it’s just had, last year, its 40th anniversary. Its remit is to disseminate research information on aspirin and arrange meetings to increase discussion about research and publicise recent developments.

What was the theme of this year’s scientific conference and why was it selected?

The theme was aspirin in the 21st century and it was really around the issue of what does aspirin do which we didn’t realise it did before? What are the new data on effects of aspirin beyond its effects just on vascular events? And how do we begin to tie together all of these different effects and come up with an overall balance of risk and benefit.

What research have you been involved in with regards to the use of aspirin?

We do a lot of research on patients at risk of stroke, so patients with mini-strokes, TIAs or warning strokes, and we found very large effects of aspirin in the acute phase in preventing major stroke. In that particular patient group aspirin reduces the risk of stroke in the next few months by about 70%. So in that situation it’s a highly effective drug in terms of preventing vascular events. We’ve also done quite a lot of work on the much longer-term effect of aspirin on the risk of cancer and particularly colon cancer and we and others have shown that if you take aspirin for about five years it reduces the risk of colon cancer by about half. But there is a delay of about ten years before you actually see that effect because it’s acting on the very early development of cancers so that it’s only ten years later when that benefit becomes clinically obvious.

What have been some of the highlights of today’s meeting?

There was a lot of interest in understanding the mechanisms of the effect of aspirin, particularly on colon cancer. We know a lot about how aspirin prevents vascular events by acting on platelets but there’s still uncertainty about how it works in terms of the colon and cells that might be at risk of developing cancers. There were some very interesting data presented on how low dose aspirin does change the biochemistry and the physiology of cells in the healthy colon in ways that might explain its effect on cancer risk.

Is the mechanism of aspirin in colorectal cancer different to the mode of action in the vascular system?

It probably has a different mechanism, it’s certainly different in terms of the latency, so how long you have to take aspirin for to see a benefit. In terms of vascular events aspirin reduces the risk immediately on the first day that you take an aspirin whereas for cancer it’s a much more long-term calculus in terms of whether it’s worthwhile or not.

Can you comment on why aspirin has such a broad clinical role?

Partly, I think, because what aspirin does is, over and above its effect on platelets, it reduces inflammation. Inflammation is a process that’s involved in so many different diseases, cancer being one of them, that a drug that reduces inflammation will undoubtedly have effects on a whole host of different diseases, potentially some good and some bad. I think we’re probably only scratching the surface at the moment about what aspirin does.

What is the future of aspirin?

One of the key issues is the on-going trials because one of the important questions that people ask is, well, aspirin prevents vascular events, it has an effect on cancer, it also has some risks in terms of bleeding, should I take it as an individual? I think one of the difficulties is that the old trials that were done in the 1980s and the 1990s probably no longer apply at the moment because blood pressure is now better controlled, people are on statins, smoking rates are lower, there are all sorts of differences. So we’re quite excited to see the results of the ongoing trials, the ARRIVE trial and the ASCEND trial and the ASPREE trial to see what aspirin does in the 21st century, as it were, rather than the 20th century.

Could you tell us more about the trials you just mentioned?

The ARRIVE trial is looking at aspirin in relatively healthy people that haven’t had a previous vascular event but are at slightly increased risk. So are they a group who would get sufficient benefit from taking aspirin because their vascular risk is increased? That’s a trial of 1,200 patients, half on aspirin, half on placebo, treated for six years that will report next year. Then there’s a similar sized trial in diabetics, the ASCEND trial, and then a variation of the trial in Australia, predominantly, the ASPREE trial looking at the balance of risk and benefit of aspirin in a much more elderly patient population, in their 70s and 80s, late 70s and 80s.

What about some of the trials of using aspirin in oncology?

The work that we did and others did showing that there seemed to be some effects of aspirin on risk of metastasis and risk of recurrence of cancer has led to several new trials looking at if you have a cancer diagnosed and you have the initial treatment then if you take aspirin after that does that improve your long-term survival. The Add-Aspirin trial is the biggest which is just starting to recruit in the UK and there’s the ASCOLT trial in Asia and several other new trials that are just getting going.

What’s the take-home message?

I think if you’ve got existing vascular disease then the evidence is that it’s definitely worth taking aspirin, the benefits outweigh the risks. If you’ve got a strong family history, perhaps, of particularly colon cancer or if you’ve got a genetic syndrome that makes you prone to colon cancer, Lynch Syndrome, then it’s worth taking aspirin. I think the jury is still out if you’re otherwise healthy whether the benefits outweigh the risks and I think we still need to get better data on that.