Aspirin and cancer: Evidence from randomized trials


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Nancy Cook
Brigham and Women's Hospital & Harvard Medical School, Boston,USA

Abstract

The role of aspirin in prophylaxis remains complex. Aspirin leads to an apparent 12% reduction in cardiovascular disease (CVD) in primary prevention, but evidence has emerged that it may also reduce cancer, primarily colorectal cancer. Pooled data from trials of daily aspirin over 20 years of follow-up found a 24% reduction in colorectal cancer incidence and a 35% reduction in colorectal cancer mortality, with the effect emerging after 5-10 years. All-cause cancer death was reduced by 21%, with a stronger effect for gastrointestinal cancer. Benefits increased with duration of aspirin use, with an earlier effect in trials using a higher dose. Recent meta-analyses found reductions in fatal plus non-fatal cancer at several sites after only three years. Larger effects were seen for metastatic cancer, particularly metastatic adenocarcinoma.

Using an alternate-day dose, extended 12-year follow-up in the Physicians’ Health Study found no association with colorectal cancer. The Women’s Health Study found no effect on cancer, including colorectal cancer, over a 10-year treatment and follow-up. In a 7-year extension, however, incidence of colorectal cancer was 18% lower in the active group, with the effect emerging after 10 years.

Adverse effects of aspirin include risk of bleeds. Meta-analyses of trials have found a 32-67% increase in hemorrhagic stroke, 74% in fatal hemorrhagic stroke, and 54% increase in extracranial bleeds. While fatal events are rare, incidence of nonfatal bleeds is higher. The net benefits of aspirin for both CVD and cancer must be weighed against increased bleeds, including peptic ulcer and impact on quality of life.

Overall, trial data suggest effects of aspirin primarily on colorectal cancer, with possible effects on other sites. The effects on cancer appear to occur at all doses, including alternate day use, with earlier effects seen at larger doses. Potential mechanisms need to address effects with infrequent low-dose use.