The US Preventive Services Task Force (USPSTF) recommends low-dose aspirin use for the prevention of cardiovascular disease among average-risk individuals aged 50 to 59 years with a 10% or greater 10-year risk of cardiovascular disease (1). Long-term regular aspirin use is also associated with reduced risk of obesity- and inflammation-associated cancers, particularly colorectal cancer (CRC) (2,3). Numerous follow up trials have consistently demonstrated significant reductions in risk in GI cancers – the NIH-AARP (4), the Nurses Health Study (5) and the Health Professionals Follow-up study (6,7). However, evidence linking aspirin to reduction of other cancers is limited.
The Aspirin in Reducing Events in the Elderly (ASPREE) study 13 was a randomised clinical trial conducted in the United States and Australia to investigate the efficacy of 100mg of aspirin daily vs placebo in extending disability-free survival among elderly individuals (recruitment age 65 years or 70 years) during 4.7 years of follow-up unexpectedly found an increase in all cause and cancer related deaths with aspirin (8). Suddenly, the evidence of the benefits of aspirin in reducing cancer mortality is on uncertain footing again.
The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was designed to determine in screenees ages 55–74 at entry whether screening with flexible sigmoidoscopy (60-cm sigmoidoscope) can reduce mortality from colorectal cancer, whether screening with chest X-ray can reduce mortality from lung cancer, whether screenng men with digital rectal examination (DRE) plus serum prostate-specific antigen (PSA) can reduce mortality from prostate cancer, and whether screening women with CA125 and transvaginal ultrasound (TVU) can reduce mortality from ovarian cancer (9).
Data from the trial was analysed post hoc to explore the association of aspirin use with mortality risk among older adults enrolled in the trial (10). At enrolment, participants were asked “During the last 12 months, have you regularly used aspirin or aspirin-containing products, such as Bayer, Bufferin, or Anacin.” If they answered yes, the frequency of usage was also recorded.
Of the 146 152 participants, 40 419 individuals (27.7%) died during follow-up, including 12 421 individuals (30.7%) who died of any cancer, 1425 individuals (3.5%) who died of GI cancers (including 353 individuals with esophageal cancer [2.8%] and 258 individuals with gastric cancer [2.1%]), and 814 individuals (6.6%) who died of CRC.
Aspirin use among individuals 65 years and older was associated with a lower risk of mortality. This observation was consistent across all causes of mortality (ie, all-cause, cancer, GI cancer, and CRC); however, the greatest reduction in risk was noted for CRC mortality among individuals who used aspirin 3 or more times per week.
Participants in the PLCO Cancer Screening Trial who were underweight (ie, BMI <20) had no observable benefit associated with aspirin use, while those with BMI 20 or higher were associated with reduced mortality risk, particularly with aspirin use 3 or more times per week. reduced risk of CRC mortality was only associated with individuals with BMI 20 to 29.9 who reported aspirin use 3 or more times per week.
Aspirin use 3 or more times per week was associated with a reduction in all-cause, cancer, GI cancer and CRC mortality in older adults. Individuals with higher BMI (20-29) appears to have benefit than individuals with lower BMI.
- Bibbins-Domingo K; US Preventive Services Task Force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: US Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016;164(12):836-845. doi:10.7326/M16-0577
- Cuzick J. Preventive therapy for cancer. Lancet Oncol. 2017;18(8):e472-e482. doi:10.1016/S1470-2045(17) 30536-3
- Rothwell PM, Wilson M, Elwin C-E, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet. 2010;376(9754):1741-1750. doi:10.1016/S0140-6736(10)61543-7
- Shebl FM, Hsing AW, Park Y, et al. Non-steroidal anti-inflammatory drugs use is associated with reduced risk of inflammation-associated cancers: NIH-AARP study. PLoS One. 2014;9(12):e114633. doi:10.1371/journal.pone. 0114633
- Chan AT, Giovannucci EL,Meyerhardt JA, Schernhammer ES, Curhan GC, Fuchs CS. Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. JAMA. 2005;294(8):914-923. doi:10.1001/jama.294.8.914
- Khalaf N, Yuan C, Hamada T, et al. Regular use of aspirin or non-aspirin nonsteroidal anti-inflammatory drugs is not associated with risk of incident pancreatic cancer in two large cohort studies. Gastroenterology. 2018;154(5):1380-1390.e5. doi:10.1053/j.gastro.2017.12.001
- Cao Y, Nishihara R,Wu K, et al. Population-wide impact of long-term use of aspirin and the risk for cancer. JAMA Oncol. 2016;2(6):762-769. doi:10.1001/jamaoncol.2015.6396
- 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;379(16):1499-1508. doi:10.1056/NEJMoa1800722
- Andriole GL, Crawford ED, Grubb RL III, et al; PLCO Project Team. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up. J Natl Cancer Inst. 2012;104(2):125-132. doi:10.1093/jnci/djr500
- Holli A. Loomans-Kropp, PhD, MPH; Paul Pinsky, PhD; Yin Cao, ScD, MPH; Andrew T. Chan, MD, MPH; Asad Umar, PhD, DVM. Association of Aspirin Use With Mortality Risk Among Older Adult Participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. JAMA Network Open. 2019;2(12):e1916729. doi:10.1001/jamanetworkopen.2019.16729