Lengthy Aspirin Use Linked to Reduced Heart Deaths in Women

BOSTON, March 26 -- Healthy women who took low-to-moderate doses of aspirin for at least five years had a reduced risk of death from any cause but especially cardiovascular disease, according to a large observational study.

Women who reported using aspirin currently had a 25% lower risk of all-cause death compared with those who never used aspirin regularly, reported Andrew Chan, M.D., of Harvard Medical School here, and colleagues, in the March 26 issue of the Archives of Internal Medicine.

The association was stronger at five years, with a 38% reduced risk of death from cardiovascular disease, while at 10 years the cancer death risk was 12% lower for aspirin users, said

The data came from a prospective, nested, case-control study of 79,439 women enrolled since 1980 in the Nurses' Health Study who had no history of cardiovascular disease or cancer.

All told, there were 9,477 deaths from any cause during 24 years of follow-up, with 1,991 deaths from cardiovascular disease, and 4,469 from cancer.

In an accompanying editorial, John A. Baron, M.D., of Dartmouth Medical School in Lebanon, N.H., sounded a skeptical note.

He pointed out that the Women's Health Study, carried out during more than 11 years and including 40,000 women, found no effect on cardiovascular or other mortality in healthy women, leaving confusion about aspirin's role.

"Is aspirin really that good or is there some other explanation for the findings that differ so much from those of the WHS and other primary prevention trials?" he asked.

In the current study, the investigators assessed the relative risk of death according to aspirin use before diagnosis of incident cardiovascular disease or cancer and during the corresponding period for each control subject.

The apparent benefit was largely confined to low-to-moderate doses of aspirin (one to 14 standard tablets a week), whereas higher doses (more than 14 tablets) were not beneficial.

Among women who reported current aspirin use, the multivariate relative risk of all-cause death was 0.75 (95% confidence interval, 0.71-0.81) compared with women who never used aspirin regularly.

The risk reduction was more apparent for death from cardiovascular disease (RR, 0.62, CI, 0.55-0.71), than for cancer deaths (RR, 0.88, CI, 0.81-0.96).

Use of aspirin for one to five years was associated with significant reductions in cardiovascular mortality (RR, 0.75; CI, 0.61-0.92). In contrast, a significant reduction in risk of cancer deaths was not observed until after 10 years of aspirin use (P for linear trend=.005).

The lower risk of cancer deaths was statistically significant for death from colorectal cancer (multivariate RR, 0.72, CI, 0.56-0.92), they reported. Although current aspirin use did not seem to confer an overall significant benefit for breast or lung cancer deaths, women who used aspirin for longer than 20 years seemed to have a modest benefit for these cancers, the researchers said.

The benefit associated with aspirin was confined to low and moderate doses and was significantly greater in older participants (P for interaction

The researchers wrote that because the study was observational, "these results should be interpreted cautiously and are insufficient evidence to alter current clinical recommendations. Nevertheless, these data support a need for continued investigation of the use of aspirin for chronic disease prevention."

In his editorial, Dr. Baron noted that the difference between the Nurses' Health Study and the aggregated data from the Women's Health Study and other trials is too large to be explained by potential weaknesses in the randomized studies.

"At the same time," Dr. Baron wrote, "one has to consider that the observational NHS may not have been able to deal with the

differences between aspirin users and nonusers."

Although the common finding in both studies of enhanced effects in older women leaves room for the possibility that aspirin reduces cardiovascular mortality in those patients, a large reduction in cardiovascular mortality in middle-aged women seems unlikely, he said.

"Therefore, these new findings by Chan et al cannot overcome the accumulated evidence that aspirin is not particularly effective for the primary prevention of death from cardiovascular disease in women," Dr. Baron concluded.

Dr. Baron, the editorial writer, reported no financial disclosures.