ASPREE (ASPirin in Reducing Events in the Elderly) was a randomized, placebo-controlled trial of aspirin (100 mg enteric coated daily) versus placebo in people aged 65 + years and free of cardiovascular events at recruitment. A total of 19,114 Australians and Americans, screened to confirm normal cognition and no prior cardiovascular event at study entry, were recruited and followed on average for 4.7 years. The first three outcome papers for the study have just been published on 16th September 2018 in the New England Journal of Medicine. The risk of death was greatest in the aspirin-treated group versus the placebo group: 12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group (hazard ratio 1.14; 95% confidence interval (CI), 1.01–1.29) . The main contribution to the higher death rate in the aspirin group was cancer (hazard ratio 1.31, 95% CI 1.10–1.56). This was not confined to a specific cancer, although a higher rate of colon cancer was an important contributor (hazard ratio 1.77, 95% CI 1.02–3.06). Of note, intracranial bleeding was more likely with aspirin than with placebo (hazard ratio 1.50; 95% CI, 1.11–2.02), with no specific effect by subgroup analyses. The hazard ratio for a major secondary hemorrhage for women was 1.58 (95% CI 1.26–1.99). In addition, a cardioprotective effect was not seen (aspirin versus placebo hazard ratio, 0.89; 95% CI 0.77–to 1.03).
This large, robust, randomized, placebo-controlled clinical trial has clearly shown that aspirin, commenced at 65 + years, did not prevent cardiovascular disease or cancer, but unexpectedly was associated with increased total cancer risk and increased all-cause mortality. Furthermore, in a separate paper, concurrently published in the New England Journal of Medicine, aspirin was not associated with increased disability-free survival . In women, past observational studies have suggested that aspirin and other anti-inflammatory drugs might protect women from breast cancer, with a risk reduction in the order of 10–20% . This was not seen for the 10,783 female participants in ASPREE.
Recently, Kuo and colleagues reported an apparent protective effect of aspirin against colon cancer in a case-controlled study of 65,208 colorectal cancer cases and 65,208 matched controls , a finding not supported by ASPREE. This highlights that epidemiological studies can suggest association but robust, adequately powered, randomized, placebo-controlled trials are essential before a treatment benefit or ill effect can be established. The three ASPREE papers now published are each available as open access and certainly make for informative reading [1, 2, 5].
Susan R. Davis
Professor of Women's Health and NHMRC Senior Principal Research Fellow, Director, Women's Health Research Program, President, International Menopause Society; Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University Australia
- McNeil JJ, Nelson MR, Woods RL, et al.; ASPREE Investigator Group. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med 2018 Sep 16. Epub ahead of print
- McNeil JJ, Woods RL, Nelson MR, et al.; ASPREE Investigator Group. Effect of aspirin on disability-free survival in the healthy elderly. N Engl J Med 2018 Sep 16. Epub ahead of print
- Zhao YS, Zhu S, Li XW, et al. Association between NSAIDs use and breast cancer risk: a systematic review and meta-analysis. Breast Cancer Res Treat 2009;117:141-50
- Kuo CN, Pan JJ, Huang YW, Tsai HJ, Chang WC. Association between nonsteroidal anti-inflammatory drugs and colorectal cancer: a population-based case-control study. Cancer Epidemiol Biomarkers Prev 2018;27:737-45
- McNeil JJ, Wolfe R, Woods RL, et al.; ASPREE Investigator Group. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med 2018 Sep 16. Epub ahead of print
Content updated 8 October 2018