full article (copy see below) paid for and stored on crabsallover PC: Moayyedi and Jankowski 341bmj-rothwell-aspirin-cancer.pdf. Further, crabsallover reviewed this article here in some depth.
Cite this as: BMJ 2010; 341:c7326
- Editorial
Does long term aspirin prevent cancer?
- Paul Moayyedi, professor of medicine1,
- Janusz A Jankowski, James Black fellow2
+Author Affiliations
- janusz.jankowski@clinpharm.ox.ac.uk
The cardioprotective effects of aspirin are well established. A meta-analysis of individual subject data from primary prevention randomised controlled trials (RCTs) suggested that aspirin can reduce the relative risk of non-fatal myocardial infarction by about 20%.1 Overall, however, the risks of treatment (severe gastrointestinal and extracranial bleeding) were roughly the same as the benefits, so routine use of aspirin as a primary preventive strategy was not recommended. The meta-analysis did not evaluate any potential reduction of mortality from cancer, as has been suggested by observational data.2 Observational data are difficult to interpret, however, because associations may not be causal and may be the result of confounding or bias.3 Rothwell and colleagues have therefore conducted another meta-analysis of individual subject data from RCTs of aspirin versus no aspirin for prevention of vascular disease, but this time they evaluated mortality from cancer as the main outcome.4 They found a 21% (95% confidence interval 8% to 32%) reduction in the odds of death from cancer in people who took aspirin for almost six years, and the effect was strongest for gastrointestinal cancers. The authors suggest that this may now tip the balance in favour of using aspirin as a primary prevention strategy, both for ischaemic heart disease and cancer⇓.
Cordelia Molloy/Science Photo Library
The data initially look compelling, and primary care providers could be forgiven for now advising patients above a given age to take aspirin. Recommending widespread use of a drug in an otherwise healthy population, however, needs to be approached cautiously because we need to be certain that the benefits will outweigh the risks.1 A 20% reduction in death from cancer seems impressive, but looking at the data in terms of absolute numbers gives a different story. These trials followed up 25 750 participants for more than 150 000 patient years, and 20 fewer cancers occurred in those taking aspirin compared with those not taking aspirin. Looked at another way, after taking aspirin for almost six years there was a 0.5% absolute reduction in death from cancer, with a number needed to treat of 200 (111 to 1075). Compared with the 50% increase in risk of serious gastrointestinal and extracranial bleeding in participants taking aspirin (overall more than 100 excess serious bleeds occurred in the aspirin group in primary prevention trials),1 it is not clear that the benefits outweigh the risks, even when factoring in the cardioprotective effects of aspirin.
The most rigorous approach to assessing this is to evaluate all cause mortality. To their credit, Rothwell and colleagues analysed this in some detail and report a statistically significant reduction in all cause mortality.4Crucially, the effect is only marginally significant (relative risk of death in the aspirin arm 0.93, 0.87 to 1.00; P=0.045) (figure⇓). This is not particularly robust, especially as six of the eight trials were in subjects at high risk of cardiovascular disease, where the benefits of aspirin should be greatest. Furthermore, the authors included one RCT where the data had been destroyed.5 It could be argued that because they had intended to conduct a meta-analysis of individual participant data this trial should have been excluded. This trial (SAPAT) had the greatest effect on all cause mortality (figure),5 and when it is excluded the results are not significant (0.94, 087 to 1.01; P=0.11). This is corroborated by another meta-analysis of individual participants (95 000 subjects with 660 000 person years of follow-up), which found that aspirin had no significant effect on all cause mortality (0.95, 0.88 to 1.02; P=0.1) when used as primary prevention.1
Forest plot of all cause mortality in randomised controlled trials of aspirin versus no aspirin4
This last point emphasises the fact that Rothwell and colleagues chose a subset of all the primary and secondary prevention aspirin RCTs that have been conducted. Twenty one RCTs have evaluated about 112 000 subjects,1so Rothwell and colleagues evaluated only around 20% of all subjects. This is because they excluded several trials that did not meet their eligibility criteria (for example, insufficient length of follow-up or subjects given aspirin on alternate days). However, systematic reviews can give different conclusions depending how they are conducted, and eligibility criteria can be somewhat arbitrary.6 For example, Rothwell and colleagues report that 75 mg aspirin a day is sufficient to reduce death from cancer. If this is the case, then perhaps 325 mg every other day would also be effective, as used in the US Physicians Health Study,7 which had 22 071 participants (almost as many as Rothwell and colleagues’ entire meta-analysis). It would be interesting to see how the inclusion of this trial would affect the results.
The data are not robust enough to recommend aspirin for the general population and we still do not know the optimum dose and length of treatment.8 Key data could come from the AspECT trial,9 10 which is evaluating the effect of aspirin in preventing all causes of mortality and oesophageal adenocarcinoma. The interim analysis will be reported in 2012.
In addition, Canada and the United Kingdom have low numbers of gastroenterologists per head of population compared with other countries in the developed world.11 If most of the population started taking aspirin our gastrointestinal services might be overwhelmed. Until further evidence from RCTs is accrued, aspirin should not be recommended for everyone.
Notes
Cite this as: BMJ 2010;340:c7326
Footnotes
- Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: JJ had support for this work from Cancer Research UK, PM had no support; JJ is a consultant for Astrazeneca Oncology and PM and JJ have received Astrazeneca educational grants; JJ is chief investigator and PM is deputy chief investigator of the AspECT trial.
- Provenance and peer review: Commissioned; not externally peer reviewed.
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