Aspirin as primary prevention reduces all-cause mortality in women

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In a nested case-control study, the use of low-to-moderate doses of aspirin (ASA) in women was associated with a significant reduction in all-cause mortality.

Key Points

In a nested case-control study published in the Archives of Internal Medicine, the use of low-to-moderate doses of aspirin (ASA) in women was associated with a significant reduction in all-cause mortality.

In this study, a total of 79,439 patients who had neither cardiovascular disease nor cancer at baseline were enrolled in the Nurses' Health Study, which began in 1980 and continued through 2004. The women completed biennial questionnaires that determined risk factors, identified newly diagnosed conditions, and assessed ASA use. Those patients who died during the study period were considered the case patients and were matched with ≤8 control patients.

The primary end point was all-cause mortality; secondary end points included cardiovascular and cancer-related deaths.

There was a significant reduction in all-cause mortality among patients who reported current use of ASA compared with nonusers of ASA (RR=0.75; 95% CI, 0.71–0.81). The authors also reported a significant association between increased duration of ASA therapy and decreased all-cause mortality (P<.001).

The greatest risk reduction was observed for cardiovascular mortality (RR=0.62; 95% CI, 0.55–0.71) and was realized within the first 5 years of treatment with ASA. For death associated with all cancers, the risk reduction was still significant but of a smaller magnitude (RR=0.88; 95% CI, 0.81–0.96) and was not observed until after 10 years of ASA use.

The authors noted the conflicts apparent when comparing the results of their study with those of the Women's Health Study (WHS), a large placebo-controlled trial that investigated the effects of treatment with ASA 100 mg every other day on cardiovascular and cancer mortality on women, and with the Hypertension Optimal Treatment (HOT) study, a randomized trial that assessed the blood-pressure-lowering benefit of ASA 75 mg/d in men and women. The HOT study failed to demonstrate a statistically significant reduction in the risk of death from cardiovascular causes with the use of ASA. The WHS study concluded that ASA was not associated with a significant reduction in the risk of cardiovascular events and the development of cancer. The authors of this most recent study stated that: "The WHS study had shorter follow-up, included fewer participants and end points, and examined only a single regimen of aspirin." Additionally, the authors cited the small study size (589 deaths) and short-term follow-up (median, 3.8 y) as limitations of the HOT study.

The authors stated that the cardiovascular and cancer benefits of ASA demonstrated in their study might be caused by the agent's "effect on common pathogenic pathways such as inflammation, insulin resistance, oxidative stress and cyclooxygenase enzyme activity." Regarding cardiovascular effects, the authors also stated: "Because thrombosis and platelet aggregation are relatively acute events, it is not surprising that we observed a benefit from aspirin therapy on vascular disease within 5 years of use."

In a related editorial, John A. Baron, MD, assessed the differences among the outcomes of this and similar studies and concluded that: "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."

SOURCES

Chan AT, Manson JE, Feskanich D, Stampfer MJ, Colditz GA, Fuchs CS. Long-term aspirin use and mortality in women. Arch Intern Med. 2007;167:562–572.

Ridker PM, Cook NR, Lee IM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005;352:1293–1304.

Cook NR, Lee IM, Gaziano JM, et al. Low-dose aspirin in the primary prevention of cancer: The Women's Health Study: A randomized controlled trial. JAMA. 2005;294:47–55.

Baron JA. Can aspirin keep mortality at bay [editorial]? Arch Intern Med. 2007;167:535–536.

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