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Tuesday, 21 December 2010

Should we all take a daily dose of aspirin? asks Adam at dianthus

reposted from: http://dianthus.co.uk/should-we-all-take-a-daily-dose-of-aspirin VIA a comment Adams comment: http://scienceblog.cancerresearchuk.org/2010/12/07/expert-opinion-aspirin-and-cancer-the-unanswered-questions/

I'm Adam Jacobs, and I run Dianthus Medical Limited: making the world of medical writing, statistics and data management a better place via Adams twitter account.

crabsallover highlights in red, key points in bold red. crabsallover Comments in blue.

Should we all take a daily dose of aspirin? The lead item on the news on Radio 4 when I woke up this morning was a paper that has just been published in the Lancet on the effects of daily aspirin use on cancer deaths. This was presented as a major new piece of research that might mean we should all be taking aspirin every day. Does it? Well, it was certainly an excellent piece of research, which tells as a great deal about the effect of daily aspirin on the risk of cancer death. It seems pretty clear-cut in that respect: taking aspirin every day reduced the risk of dying of cancer (not all types of cancer, but enough types of cancer that the overall death rate from cancer was significantly reduced).

It’s important to note that this was based on data from randomised controlled trials, and is therefore much more reliable than epidemiological studies. It was also based on multiple large trials, including over 25,000 patients, so the study was large enough to be statistically robust. 

However, I don’t think this is the the end of the story for aspirin. We already knew that aspirin reduces the risk of cardiovascular disease, and we now know that it reduces the risk of cancer.

But aspirin also has harms, which need to be weighed against those benefits, the most important of which is an increased risk of gastrointestinal bleeding. The balance of benefits and harms is likely to vary from one person to another.

Someone with risk factors for cancer and heart disease but not for gastrointestinal bleeding is likely to benefit from aspirin, whereas someone with a history of gastrointestinal bleeds would be more likely to be harmed by aspirin. That is surely obvious?

I don’t see anything in this new paper that gives an unambiguous answer to how we determine who would benefit from aspirin and who wouldn’t. One important statistic in the paper was the effect on all-cause mortality, in other words not just deaths from cancer, but deaths from anything else as well. If all-cause mortality were reduced in the aspirin patients, then that would give a pretty good clue that the overall benefits outweigh the overall harms, at least in patients similar to the ones studied (although it’s still not a perfect measure, as it ignores any benefits or harms that don’t affect mortality, such as non-fatal gastrointestinal bleeding, which can seriously ruin your day even if it doesn’t kill you). 


The results here were a little inconsistent. In-trial all-cause mortality (ie deaths among patients who were still taking part in the trials at the time of death) was slightly, but significantly reduced, from 11.1% to 10.2%., P = 0.047. 


Taking account of deaths occurring after the trials as well, mortality was significantly reduced after 15 years of follow-up (hazard ratio 0.92, 95% CI 0.86 to 0.99, P = 0.03), but not after 20 years of follow-up (hazard ratio 0.96, 0.90 to 1.02, P = 0.37). 

On the whole, it does appear that aspirin reduced all-cause mortality, but the results are suggestive, rather than compelling. 

It’s also important to note that many of the patients in the trials had cardiovascular risk factors, and their all-cause mortality may have been more favourably affected than the general population, because of aspirin’s effect on cardiovascular mortality. So there is no guarantee that those figures for all-cause mortality would generalise to everyone. 

I don’t think we are quite at the point where aspirin should be recommended for everyone over the age of 50 who doesn’t have any contra-indications (such as a history of gastrointestinal bleeding). We still need a better estimate of the effect of aspirin on all-cause mortality, particularly in different groups of patients with different combinations of risk factors, as well as a better assessment of exactly what the trade-off is between non-fatal benefits and risks. 

Maybe when further research has given us those answers it will become the default position for everyone to take aspirin, although I suspect it’s always going to remain a personal choice, based on an individual assessment of the importance of different outcomes.

As for me, I’m not going to start taking aspirin every day, but I will certainly keep watching the literature with interest. Another positive paper for aspirin might just convince me that I should start taking it. 

DEC 07 2010 Written by Adam at 4:17 pm on 07/12/2010.

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