Effect of Aspirin on All‐Cause Mortality in the Healthy Elderly

BACKGROUND In the primary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, now published in the Journal, we report that the daily use of aspirin did not provide a benefit with regard to the primary end point of disability‐free survival among older adults. A numerically higher rate of the secondary end point of death from any cause was observed with aspirin than with placebo. METHODS From 2010 through 2014, we enrolled community‐dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric‐coated aspirin or placebo. Deaths were classified according to the underlying cause by adjudicators who were unaware of trial‐group assignments. Hazard ratios were calculated to compare mortality between the aspirin group and the placebo group, and post hoc exploratory analyses of specific causes of death were performed. RESULTS Of the 19,114 persons who were enrolled, 9525 were assigned to receive aspirin and 9589 to receive placebo. A total of 1052 deaths occurred during a median of 4.7 years of follow‐up. The risk of death from any cause was 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 to 1.29). Cancer was the major contributor to the higher mortality in the aspirin group, accounting for 1.6 excess deaths per 1000 person‐years. Cancer‐related death occurred in 3.1% of the participants in the aspirin group and in 2.3% of those in the placebo group (hazard ratio, 1.31; 95% CI, 1.10 to 1.56). CONCLUSIONS Higher all‐cause mortality was observed among apparently healthy older adults who received daily aspirin than among those who received placebo and was attributed primarily to cancer‐related death. In the context of previous studies, this result was unexpected and should be interpreted with caution. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583.)

[1]  R. Doll,et al.  Randomised trial of prophylactic daily aspirin in British male doctors , 1988, British medical journal.

[2]  Joël Ménard,et al.  Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial , 1998, The Lancet.

[3]  M. Roncaglioni Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general Practice , 2001, The Lancet.

[4]  A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women , 2005 .

[5]  Shuji Ogino,et al.  Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. , 2007, The New England journal of medicine.

[6]  P. Macfarlane,et al.  The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease , 2008, BMJ : British Medical Journal.

[7]  G. Moneta Low-Dose Aspirin for Primary Prevention of Atherosclerotic Events in Patients With Type 2 Diabetes: A Randomized Controlled Trial , 2009 .

[8]  P. Rothwell,et al.  Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials , 2011, The Lancet.

[9]  J. Price,et al.  Aspirin for Prevention of Cardiovascular Events in a General Population Screened for a Low Ankle Brachial Index: A Randomized Controlled Trial , 2011 .

[10]  P. Rothwell,et al.  Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials , 2012, The Lancet.

[11]  H. Putter,et al.  Competing risks in epidemiology: possibilities and pitfalls. , 2012, International journal of epidemiology.

[12]  C. Reid,et al.  Study design of ASPirin in Reducing Events in the Elderly (ASPREE): a randomized, controlled trial. , 2013, Contemporary clinical trials.

[13]  K. Shimada,et al.  Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial. , 2014, JAMA.

[14]  Yin Cao,et al.  Aspirin and colorectal cancer: the promise of precision chemoprevention , 2016, Nature Reviews Cancer.

[15]  C. Reid,et al.  The aspirin in reducing events in the elderly trial: Statistical analysis plan , 2018, International journal of stroke : official journal of the International Stroke Society.

[16]  Suzanne G. Orchard,et al.  Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly , 2018, The New England journal of medicine.

[17]  Suzanne G. Orchard,et al.  Effect of Aspirin on Disability‐free Survival in the Healthy Elderly , 2018, The New England journal of medicine.

[18]  Suzanne G. Orchard,et al.  Baseline Characteristics of Participants in the ASPREE (Aspirin in Reducing Events in the Elderly) Study. , 2019, The journals of gerontology. Series A, Biological sciences and medical sciences.