Daily Low-Dose Aspirin, Diabetes, and Age—Still Looking for a Balance | Cardiology | JAMA Network Open | JAMA Network
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Invited Commentary
June 21, 2021

Daily Low-Dose Aspirin, Diabetes, and Age—Still Looking for a Balance

Author Affiliations
  • 1DARTNet Institute, Department of Family Medicine, University of Colorado Aurora
JAMA Netw Open. 2021;4(6):e2112875. doi:10.1001/jamanetworkopen.2021.12875

According to federal surveys, aspirin is one of the most commonly taken medications in the US, with over 20% of people older than 40 years using low-dose aspirin daily.1 In JAMA Network Open, Liu and colleagues2 explore regular aspirin use in individuals older than 60 years, analyzing a number of variables related to the benefits and risks and how they relate to daily aspirin use. Their analysis of the National Health and Nutrition Examination Survey data from 2011 to 2018 highlights that aspirin usage in individuals with known cardiovascular disease (CVD) is in the 70% range, which is similar to previous estimates.3 Given that other antiplatelet medications were not included, nor were individuals with high bleeding risk accounted for, this percentage may be approaching a logical ceiling in the population included in this analysis. The benefit-to-risk ratio of daily low-dose aspirin is high in individuals with known CVD disease; thus, continued use beyond age 70 years in most individuals is clinically logical.

However, the analysis by Liu et al2 also points out that a large percentage of individuals 70 years and older take daily aspirin in the absence of known CVD. The good news is that, generally, daily aspirin use is directly proportional to overall CVD risk, with individuals who have few risk factors for CVD being the least likely to take daily aspirin compared with those with known CVD disease being the most likely use aspirin. The concern is that there is a considerable percentage of individuals at low risk for CVD who are taking aspirin therapy across all age groups. Many individuals included in this analysis may have higher risks for adverse events than for improved health outcomes.

Dating back to the 1970s, the use of aspirin for the primary prevention of acute coronary events has been considered and studied. In the past decade, aspirin use for primary prevention has been promoted by quality indicator developers, advocacy groups, and specialty societies. Yet, despite ongoing study, until recently, data indicating a clear-cut benefit of low-dose aspirin for primary prevention have been lacking. In 2016, the US Preventive Services Task Force (USPSTF) released a B recommendation (ie, at least moderate certainty for a moderate benefit) for aspirin use for primary prevention of CVD and colorectal cancer for individuals aged 50 to 59 years.4 This assessment was based heavily on 3 commissioned evidence reviews, including a meta-analysis and microsimulations, as individual trials failed to demonstrate a positive effect. For the age group older than 70 years, the USPSTF indicated that there was insufficient evidence to judge benefits vs risks.

Three new studies examining daily aspirin use and primary prevention outcomes have been published since the USPSTF statement.5-7 Combined, these studies enrolled more than 47 000 people with greater than 63% of the participants aged older than 60 years and at least 50% older than 70 years, making the results apropos to the Liu article.2 Two of the studies had no positive outcomes,5,6 either primary or secondary, and thus further support the questionable extensive use of aspirin for primary prevention in those 70 years and older. The third study, the ASCEND (A Study of Cardiovascular Events in Diabetes) trial,7 specifically enrolled individuals with type 1 or type 2 diabetes and showed a significant reduction in cardiovascular events over a period of 7.4 years (percentage of individuals, intervention vs control, 8.5% vs 9.6%; 95% CI, 0.79-0.97). Major bleeding events, a well-known adverse event with aspirin therapy at any dose, also increased as expected. Tallying the number of serious vascular events or revascularization procedures avoided and subtracting from them the number of major bleeding events caused, the results indicate that 0.34 events would be avoided per 1000 person years in the highest cardiovascular risk group, decreasing as risk decreases. Despite the overall positive outcomes, the authors concluded that it was not clear that the benefits of aspirin therapy in people at low risk for CVD outweighed the harms.7

None of the 3 studies5-7 demonstrated an improvement in mortality, either all cause or cardiovascular (depending on the study), with one, the ASPREE (Aspirin in Reducing Events in the Elderly) study,5 having higher all-cause mortality in the aspirin group. The increased deaths were primarily cancer related and downplayed by the authors, though examination of a large number of demographic and risk categories indicates that randomization appeared to have worked well, making an anomaly such as this concerning. When these 3 new studies5-7 are considered, along with the more than 95 000 individuals included in the reviews conducted for the USPSTF, the use of aspirin for the primary prevention of CVD or to lower all-cause mortality for individuals older than 70 years becomes even harder to justify. The study by Liu et al2 indicated that more than 20% of individuals in the analysis with low cardiovascular risk use daily aspirin. This percentage rises to greater than 50% of the individuals older than 80 years. This rate of aspirin use is poorly justified by current evidence and would seem likely to be causing more harm than good. That said, clinicians are left with a conundrum, because the USPSTF simulations indicate that the overall benefit from low-dose aspirin increases over time, particularly with respect to cancer prevention. Furthermore, most individuals older than 70 years using daily aspirin are not newly initiating therapy but continuing therapy started at a younger age. Stopping a therapy on which an individual appears to be doing well can be a much harder decision for both patient and clinician than not starting the treatment in the first place. Despite the concern that stopping medication may lead to worse outcomes, low-dose aspirin therapy, like all medications used by older individuals, should be regularly reviewed, and the ongoing safety and need for use should be discussed. With the addition of 3 newer studies5-7 that continue to question the efficacy of low-dose aspirin for primary prevention in older adults, this conversation has more immediacy. Only through careful, ongoing assessments can physicians make sure they are following what many consider to be the most important ethical tenet of clinical care—primum non nocere—first, do no harm.

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Article Information

Published: June 21, 2021. doi:10.1001/jamanetworkopen.2021.12875

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Pace WD. JAMA Network Open.

Corresponding Author: Wilson D. Pace, MD, Chief Medical Officer, DARTNet Institute, 12635 E Montview Blvd, Mail Box 3, Aurora, CO 80045 (wilson.pace@dartnet.info).

Conflict of Interest Disclosures: None reported.

Soni  A. Aspirin use among the adult U.S. noninstitutionalized population, with and without indicators of heart disease, 2005. Published 2007. Accessed April 4, 2021. https://meps.ahrq.gov/data_files/publications/st179/stat179.shtml
Liu  EY, Al-Sofiani  ME, Yeh  HC, Echouffo-Tcheugui  JB, Joseph  JJ, Kalyani  RR.  Use of preventive aspirin among older US adults with and without diabetes.   JAMA Netw Open. 2021;4(6):e2112210. doi:10.1001/jamanetworkopen.2021.12210Google Scholar
Fang  J, George  MG, Gindi  RM,  et al.  Use of low-dose aspirin as secondary prevention of atherosclerotic cardiovascular disease in US adults (from the National Health Interview Survey, 2012).   Am J Cardiol. 2015;115(7):895-900. doi:10.1016/j.amjcard.2015.01.014 PubMedGoogle ScholarCrossref
Bibbins-Domingo  K; US Preventive Services Task Force.  Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive Services Task Force recommendation statement.   Ann Intern Med. 2016;164(12):836-845. doi:10.7326/M16-0577 PubMedGoogle ScholarCrossref
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;379(16):1509-1518. doi:10.1056/NEJMoa1805819 PubMedGoogle ScholarCrossref
Gaziano  JM, Brotons  C, Coppolecchia  R,  et al; ARRIVE Executive Committee.  Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial.   Lancet. 2018;392(10152):1036-1046. doi:10.1016/S0140-6736(18)31924-X PubMedGoogle ScholarCrossref
Bowman  L, Mafham  M, Wallendszus  K,  et al; ASCEND Study Collaborative Group.  Effects of aspirin for primary prevention in persons with diabetes mellitus.   N Engl J Med. 2018;379(16):1529-1539. doi:10.1056/NEJMoa1804988 PubMedGoogle ScholarCrossref
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