Study: Daily aspirin may reduce risk of cancer death

reference

Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Impact of daily aspirin on the long-term risk of dying from cancer: analysis of individual patient data from randomized trials.Lancet.2011;377(9759):31-41. Epub 2010, December 6th.

design

Analysis of individual patient data from 8 studies in which aspirin (doses between 75 and 1,200 mg daily) was the interventional treatment used in cardiovascular risk reduction trials. None of the studies were designed to assess cancer incidence or cancer-related deaths. Studies were identified using public databases. All studies were randomized and had a mean planned treatment duration of at least four years or more. Randomization included aspirin versus no aspirin (no placebo given) or aspirin versus no aspirin in the presence of another antiplatelet or antithrombolytic drug (e.g., warfarin). Long-term data (20 years) were available for three studies using the UK national death certification and cancer registration systems.

Key findings

Pooled analysis of 8 aspirin trials showed a significant reduction in cancer-related deaths (674 deaths in 25,570 patients; OR 0.79, CI 0.68-0.92).P=0.003). Individual data available for 7 of the studies showed that benefit was only apparent after 5 years of follow-up (all cancer HR 0.66, CI 0.5-0.87; GI cancer HR = 0.46, CI 0.27-0.77; P = 0.003 for both groups). Data). This latent effect lasted 5 years for esophageal, pancreatic, brain, and lung cancers. An even longer latency period for a measurable reduction in deaths was found for stomach, colon and prostate cancer. The effect of aspirin was largely limited to adenocarcinomas. The benefit of aspirin was not related to the dose taken, gender or smoking status. The benefit appeared to increase with age and the duration of the aspirin intervention used in the study.

Effects on practice

Many publications suggest that taking aspirin plays a protective role in cancers of the colon, stomach, and esophagus.^1,2,3,4This is the first publication to show a significant decrease in overall cancer deaths. In addition to the strong evidence of a protective effect against gastrointestinal cancer, there is supportive evidence from several observational studies of a reduction in the incidence of prostate, ovarian, lung and brain cancer.^5.6The above-mentioned publication found that overall cancer deaths decreased by 20% among those who took aspirin long-term, and by more than 35% in lower gastrointestinal cancers in particular. This is compelling outcome data for the use of a low-cost, relatively safe intervention.

There are some important points in this study that are useful for clinicians. First, the benefit of aspirin did not correlate with the dosage used, so a minimum dose of 75 mg is expected to be sufficient to produce benefit. Second, the benefit of aspirin was a latent effect, with the reduction in deaths occurring after five years of follow-up. Third, the reduction in deaths correlated with duration of aspirin use, with longer aspirin intervention correlating with greater benefit. No benefit was seen in patients who took aspirin for less than 5 years. Finally, a reduction in deaths was noted specifically in individuals with adenocarcinoma, not in other histologic types.

Not all studies have found a protective role for aspirin in cancer development. The Nurses' Health Study, taking 100 mg every other day, showed no reduction in cancer incidence.⁷The Physician's Health Study failed to show any difference in the development of colon cancer or adenomas among those who took aspirin, although that study only lasted seven years.⁸According to the study cited above, this may not be enough as there was a 10 year latency period to reduce the number of deaths from colorectal cancer. It appears that taking aspirin daily and at a low dose for a long period of time (longer than 5 years) should be done if there is a benefit in reducing cancer incidence or cancer deaths. This means that people in their 40s or 50s may get more benefit from taking it for a longer period of time. As the authors point out, there is no indication of what to expect after 20 years.

There is enough evidence that inflammatory mediators, including cyclooxygenase-2, are involved in carcinogenic, tumorigenic and metastatic processes.⁹Looking at this study from a broader physiological perspective, one may also ask the question, “Does reducing inflammation through COX-2 inhibition affect cancer death rates?” Admittedly, it is possible that the action of aspirin is due to a different mechanism, but given the established role of inflammation in carcinogenesis, Cox-2 inhibition of aspirin is the putative mechanism so far. This is conceptually important because there are many other ways to influence inflammation, many without risk to the patient. These include whole foods, selected herbs, fish oil, stress reduction and proper sleep. To what extent is the anti-inflammatory effect of aspirin a practical substitute for more sensible dietary and lifestyle changes? This is a rhetorical question because the number of confounding factors affecting inflammation cannot be accounted for in any study design.

Widespread use of any drug should be viewed with great caution. (PULLEDQUOTE) While low-dose aspirin carries some risk of stomach irritation and bleeding, the data in the above publication are compelling because this risk appears minimal compared to the benefits for most people. However, the risk of bleeding - especially gastrointestinal bleeding - should be examined in every patient.

Study Restrictions

These data come from studies that originally evaluated aspirin as a primary or secondary intervention for cardiovascular disease/events. The studies were not designed to assess the effects of aspirin on cancer incidence or mortality. Furthermore, the data is only as good as the source, and death certificates may or may not accurately list cancer as the cause of death. For example, a cancer patient may die as a result of the disease or treatment (e.g. infection, stroke) and this complication may be documented as the actual cause of death. Prospective studies are needed to support the conclusions of the above study.

As all longer-term (20-year) data come exclusively from UK databases, there are some dietary biases that may not be applicable to other populations. The authors acknowledge that “the benefit of aspirin may be reduced in populations with high dietary intake of salicylates.” Assessing salicylate intake at baseline and throughout the study may be helpful in the future.

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