October 31, 2011 (Boston, Massachusetts) — A low daily dose of aspirin can reduce the risk for cardiovascular events, and recent data also show that it might reduce cancer-specific mortality.

However, researchers from the American Cancer Society (ACS) caution that the actual rate of risk reduction is still unclear, and that it is too early to make recommendations.

A recent pooled analysis of 8 randomized trials of daily aspirin for the prevention of vascular events reported a dramatic 34% reduction in overall cancer mortality after 5 years. The effects were similar and independent of dose, sex, and smoking (Lancet. 2011;377:31-41).

However, a study from the ACS, presented here at the Tenth Annual American Association for Cancer Research International Conference on Frontiers in Cancer Prevention Research, found that although aspirin use was associated with less cancer mortality, the reduction in cancer mortality was much smaller than that seen in the pooled analysis.

Differences in Results

"We wanted to see if we could validate the results from the [pooled] analysis, and we wanted to see if we could help clarify the degree to which aspirin might reduce the risk of cancer," Eric J. Jacobs, PhD, strategic director of pharmacoepidemiology at the ACS, told Medscape Medical News. "In our large study, we did in fact find a reduction in overall mortality and about a 15% reduction in overall cancer mortality, which is about half of what was seen in the [pooled analysis]."

There are a number of possible reasons for this difference in results, explained Dr. Jacobs. "One possibility is the size of the studies," he said. "Results can also vary by chance, and the number of people in both studies was somewhat limited."

"Another reason is that the [pooled] analysis consisted of randomized trials; we were looking at observational data, so there could be some bias in our study," he added. "The exact amount of reduction remains to be seen, I think."

Evidence that supports a strong effect of aspirin on overall cancer mortality is limited, the researchers note. Although observational studies of aspirin use have shown a substantially reduced risk for colorectal, esophageal, and stomach cancer, they have not supported strong effects on cancer outside the gastrointestinal tract.

Lower Risk Reduction Seen

There were 674 cancer-related deaths in the 25,570-patient cohort in the pooled analysis. There was also a 21% reduction in the number of cancer-related deaths in those who had taken aspirin, compared with those who had not.

The pooled results also showed that the benefits of taking aspirin increased over time. After 5 years, the mortality rate declined by 34% for all cancers and by 54% for gastrointestinal cancers.

Dr. Jacobs and colleagues sought to better quantify the association between daily aspirin use, particularly long-term use, and cancer mortality. Their cohort involved 100,140 men and women who participated in the Cancer Prevention Study II Nutrition Cohort and who had no history of cancer. Hazard ratios were calculated, and adjustments were made for age, sex, race, education, smoking, physical activity, heart disease, stroke, diabetes, hypertension, use of cholesterol-lowering drugs, historic use of aspirin reported in 1982, use of nonsteroidal anti-inflammatory drugs, and history of colorectal endoscopy.

Baseline aspirin use was defined by use that was reported in 1992 and 1997. Individuals who reported daily use in both years were considered to have been daily users for 5 or more years. Those reporting daily use only in 1997 were considered to have been daily users for less than 5 years.

There were 5138 cancer deaths during the follow-up period, from 1997 to 2008. The daily intake of aspirin at baseline in 1997, compared with no aspirin use, was associated with slightly less cancer mortality (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.86 to 1.00). This was not statistically significant, note the researchers, and did not vary with duration of daily use (HR, 0.93; 95% CI, 0.85 to 1.01 for less than 5 years of use; and HR, 0.94; 95% CI, 0.85 to 1.03 for 5 or more years of use).

In time-dependent analyses, which involved 3373 cancer deaths and used updated information from periodic follow-up questionnaires, the daily use of aspirin was associated with less cancer mortality, but these results also did not differ with duration of use (HR, 0.84; 95% CI, 0.76 to 0.94 for less than 5 years of use; and HR, 0.85; 95% CI, 0.76 to 0.96 for 5 or more years of use).

The associations between daily aspirin use and cancer mortality appeared to be similar for low-dose and adult-strength aspirin.

Too Early for Recommendations

"The main reason for aspirin use in this cohort was that the participants were at a high risk of heart disease, which is not a strong risk factor for most types of cancer," said Dr. Jacobs. "This analysis adjusts for that."

The researchers note that these results do not support an effect as large as the one observed in the pooled analysis, and recommend that caution be used when applying risk estimates for long-term daily aspirin use from the pooled analysis to risk/benefit analyses.

"At this point, there has been a lot of new data coming out and that will be coming out. I think it's going to take some time for expert panels to total the evidence, and then there may well be recommendations coming out," said Dr. Jacobs.

Tenth Annual American Association for Cancer Research (AACR) International Conference on Frontiers in Cancer Prevention Research. Abstract A93. Presented October 23, 2011.


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