Friday February 6 2009
Aspirin has some benefits but taking it frequently can be harmful to health
“Taking aspirin just once a year could lower the risk of stomach cancer by more than a third,” says the Daily Mail in one of several media reports claiming that aspirin can cut the risk of developing the disease.
The study behind these reports followed over 300,000 people aged over 50 for seven years, comparing their use of aspirin and other types of pain-relief drugs with rates of stomach and oesophagus cancer. The researchers found that the risk of a certain type of stomach cancer was 36% lower among people who had used aspirin at least once in the previous 12 months.
While the researchers did find that stomach cancer risk was reduced 36% in those who took any aspirin, this result applied to the group overall, not necessarily to the group that used aspirin infrequently, as newspaper reports might imply. In fact, this was a dose-response benefit, meaning that more frequent use of aspirin had a more protective effect against cancer.
Although taking aspirin can have benefits, high-frequency use can increase the risk of serious health problems. The researchers themselves caution against daily aspirin use, saying that “the expected benefits do not outweigh the risks” for the general population. Members of the public should consult their doctor before regularly taking aspirin on the basis of this study or subsequent media reports.
Where did the story come from?
Dr Christian Abnet and colleagues from the National Cancer Institute in the US carried out this research. The study was funded by the National Cancer Institute and published in the British Journal of Cancer.
What kind of scientific study was this?
This was a prospective cohort study on the effects of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) on risk of gastric or oesophageal cancers. According to some previous studies, aspirin may prevent certain forms of stomach and oesophageal cancer.
The authors of this new research say few previous studies have used prospective data or have been able to account for other factors that may contribute towards oesophageal (gullet) and stomach cancer.
There are two main types of gastric cancer: upper gastric cancer (cardia) and lower gastric cancer (non-cardia). The researchers were interested in the effects of aspirin on the risk of each of these types.
This study is based on data from a large prospective cohort study, which investigated the link between the risk of cancer and diet and other factors. This was the NIH-AARP Diet and Health Study, conducted by the National Institute for Health in conjunction with a group formerly known as the American Association of Retired Persons (AARP). The AARP is a large, non-profit organisation that represents the interests of people over 50.
Between 1995 and 1996, 3.5 million AARP members from across eight US states received a questionnaire. This initial baseline questionnaire, given at entry into the study, asked people for their demographic details, and information on smoking, alcohol, education and food consumption. A total of 617,199 people responded to this.
They were then contacted again between 1996 and 1997 for additional information, including use of NSAID medication. Both over-the-counter and pharmacy-provided NSAIDs were included.
The respondents were specifically asked about frequency of aspirin and non-aspirin NSAID use (e.g. ibuprofen) in the previous 12 months. Frequency was originally recorded as less than twice a month, two to three times a month, once or twice a week, three to four times a week, five to six times a week, once a day, or twice or more per day. However, because there were small numbers in some of these response categories, researchers grouped users under monthly, weekly or daily.
After excluding non-responders, those with incomplete information, and those with cancer at the second questionnaire, 311,115 people (180,377 men and 130,778 women) were available for analysis. Each year until 2003, incidence of death or cancer was determined by linking their records to social security records, a cancer registry and responses to the questionnaires. Cancers were classified according to their type and site.
Researchers compared the number of cases of stomach and oesophageal cancer occurring within aspirin and NSAID categories from the 1996/1997 questionnaire until the end of follow-up in 2003. They took into account factors that may be linked to these cancers in their analyses, including age, sex, smoking, alcohol, education, diet, BMI and physical activity.
In addition, the researchers conducted a systematic review and meta-analysis of literature that had previously explored the link between aspirin use and these cancers. They report summary findings from this.
What were the results of the study?
The NIH-AARP study found that in the 12 months prior to the questionnaire, 73% of participants had used aspirin and 56% had used non-aspirin NSAIDs. Twenty-five per cent of the individuals questioned used aspirin daily.
Any use of aspirin appeared to protect against gastric non-cardia cancer (lower stomach cancer): those taking any aspirin were 0.64 times (36%) less likely to have this cancer than those who did not take aspirin at all (HR 0.64, 95% CI 0.47 to 0.86). This link was dose-dependent, i.e. taking more aspirin was more protective against cancer. Daily use was associated with a 43% reduction in risk for this type of stomach cancer (HR 0.57, 95% CI 0.39 to 0.85).
Use of non-aspirin NSAIDs also reduced risk by 0.68 times, but this was not dose-dependent. There was no effect of either aspirin or non-aspirin NSAIDs on oesophageal cancer or on gastric cardia cancer (upper stomach cancer).
The meta-analysis of 17 studies found that aspirin appeared to protect against non-cardia and oesophageal cancers, but not gastric cardia cancer. Other NSAIDs protected against all of these cancer types.
What interpretations did the researchers draw from these results?
The researchers conclude that reported use of aspirin or non-aspirin NSAIDs was linked to a 36% reduction in risk of non-cardia gastric cancer, and that this result is consistent with the earlier studies collected in researchers’ meta-analysis of 49 risk estimates in 17 other observational studies.
They say that this consistency “may warrant a randomised trial in a suitable population at high risk of the disease” with close monitoring for side effects.
Although they found no significant link between cardia (upper) gastric cancer and use of the medications investigated (while the meta-analysis did), their estimates are similar to the summary findings, although the study confidence intervals are wider.
While other studies have found that daily aspirin protects against oesophageal cancer too, this study did not. The authors were unable to explain this discrepancy.
What does the NHS Knowledge Service make of this study?
This cohort study has confirmed that regular aspirin use protects against lower gastric cancer. The study was large, and followed up participants for a reasonable length of time while collecting information on factors (confounders) that may also be linked to stomach cancer. The results were consistent with the findings from other studies, as confirmed by the researchers in their separate systematic review and meta-analysis.
There are some important points to raise:
- The report by some newspapers that taking aspirin ‘once a year’ cuts risk by a third is a slight over-extrapolation of the results. Researchers compared the ‘any use of aspirin in the previous 12 months’ group versus the ‘no aspirin use in the previous 12 months’ group, and found that the ‘any use group’ (all monthly, weekly and daily users) had an overall 36% reduced risk of lower gastric (cardia) cancer.
- The fact that there was evidence of a dose response, i.e. that risk was reduced more by more frequent use of aspirin suggests that there is likely to be an optimum frequency of use at which harms and benefits are balanced. More research is needed to establish precisely what this optimum frequency is, and to whom it applies: any harmful or beneficial effects from these drugs might vary among individuals with other risk factors for stomach or oesophageal cancers, such as smokers or those with H. pylori infection.
- In their discussion, the researchers highlight that daily aspirin use carries the risk of gastrointestinal bleeding and haemorrhagic stroke, and that “the expected benefits do not outweigh the risks”. Some newspapers rightly point out the potential for adverse events, and they quote experts who say that it is far too early to recommend regular use of aspirin to prevent cancer. There is still a lot to learn about the balance of benefits and harms, and whether this varies for different risk groups.
- A reduction in risk of 36% sounds large, but the absolute reduction (how many people avoid cancer) should also be considered. In this study, using any quantity of aspirin in the previous 12 months reduced the annual rate of non-cardia gastric cancer from 11 cases in 100,000 to seven cases in 100,000. This means that four in a 100,000 people (or one in 25,000) avoided gastric cancer by taking aspirin compared to not.
The benefits to people with heart disease from taking aspirin are already clear. These new findings will lead to further research that will determine whether benefits of regular aspirin use outweigh the well-documented harms (preferably such further research will be based on the randomised controlled trials called for by researchers and other experts in the field).
Until then, people should speak to their doctors before taking aspirin or NSAIDs regularly.