Spring 2021 Newsletter
By Katharine Stockton, Pharm.D. and Lisa C. Hutchison, PharmD, MPH
University of Arkansas for Medical Sciences (UAMS) College of Pharmacy
Heart disease and stroke are leading causes of death in older adults.1 For prevention of cardiovascular disease, aspirin works as an antiplatelet through inhibition of cyclooxygenase-1 and 2 enzymes. It irreversibly inhibits the formation of thromboxane A2 via acetylation of platelet cyclooxygenase, which then inhibits platelet aggregation.7 Aspirin is proven effective for secondary prevention of cardiovascular diseases including coronary artery disease (CAD), peripheral artery disease (PAD), and stroke/transient ischemic attack (TIA).2-6 However, the benefit to risk ratio of aspirin for primary prevention of cardiovascular disease is not as favorable given aspirin’s potential to cause bleeding.
Prior to the 2019 guidelines update from American College of Cardiology (ACC) and American Heart Association (AHA), aspirin was recommended for primary prevention of cardiovascular disease by these groups and other revered organizations8,9 However, the 2019 ACC and AHA give more cautious recommendations regarding aspirin for primary prevention10:
- Low-dose aspirin (75-100mg daily) might be considered for the primary prevention of ASCVD among select adults 40-70 years of age who are at a higher ASCVD risk but not at an increased risk of bleeding.
- Low-dose aspirin (75-100mg daily) should not be administered on a routine basis for the primary prevention of ASCVD among adults > 70 years of age.
- Low-dose aspirin (75-100mg daily) should not be administered for the primary prevention of ASCVD among adults of any age who are at increased risk of bleeding.
This update to guidelines and change from previous recommendations stems from recently published studies on the use of aspirin in the elderly.10 A series of articles from the Aspirin in Reducing Events in the Elderly (ASPREE) study were published in 2018. 11-13 The ASPREE study enrolled people 70 years of age or older who did not have cardiovascular disease, dementia, or any physical disability. Subjects were randomized to receive either aspirin or placebo. Aspirin use did not prolong disability-free survival over a period of 5 years in the intervention group as compared to placebo (P=0.79).11 However, aspirin increased all-cause mortality in the elderly compared to placebo (1.14, CI 1.01 – 1.29).12 This was attributed to cancer-related death and was an unexpected result of the study that should be interpreted cautiously given the confidence interval.
The ASPREE study also evaluated the effect of aspirin on cardiovascular events and bleeding. Cardiovascular disease was defined as a composite of fatal coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal stroke, or hospitalization for heart failure. The study found no significant difference in the rate of cardiovascular disease with 10.7 events per 1000 person-years in the aspirin group and 11.3 events per 1000 person-years in the placebo group (0.95, CI 0.83 – 1.08). However, there was a significant difference noted in the composite rate of major hemorrhage for those in the aspirin group (1.38, CI 1.18-1.62; P < 0.001).13 Specifically, a significant difference was identified in subdural or extradural hemorrhage (1.79, CI 1.06-3.02) and upper gastrointestinal bleeding (1.87, CI 1.32-2.66). It is important to note that the ASPREE trial evaluated use of aspirin in the “healthy elderly” and did not meet the expected rate of cardiovascular events; therefore the potential cardiovascular advantages may be underestimated.13 However, the results of the ASPREE trial are similar to a recent meta-analysis evaluating use of aspirin for primary prevention in adults, which also concluded aspirin use did not significantly reduce cardiovascular endpoints, but was associated with an increased risk of bleeding.14
Given these study results and recent guideline updates, use of aspirin for primary prevention in the geriatric population should be carefully considered. Clinicians should evaluate patient history, cardiovascular risk factors, bleeding risk in discussion with older adults before recommending, starting, or continuing aspirin in patients greater than 70 years old.
- FastStats – Deaths and Mortality. Centers for Disease Control and Prevention. Published 2019. https://www.cdc.gov/nchs/fastats/deaths.htm
- Winstein CJ, Stein J, Arena R, et al. Guidelines for Adult Stroke Rehabilitation and Recovery: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association . Stroke. 2016;47(6):e98-e169. doi:10.1161/STR.0000000000000098
- Kulik A, Ruel M, Jneid H, et al. Secondary prevention after coronary artery bypass graft surgery: a scientific statement from the American Heart Association. Circulation. 2015;131(10):927-964. doi:10.1161/CIR.0000000000000182
- Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016;37(29):2315-2381. doi:10.1093/eurheartj/ehw106
- Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016;68(10):1082-1115. doi:10.1016/j.jacc.2016.03.513
- Conte MS, Bradbury AW, Kolh P, et al. Global vascular guidelines on the management of chronic limb-threatening ischemia . J Vasc Surg. 2019;69(6S):3S-125S.e40. doi:10.1016/j.jvs.2019.02.016
- Aspirin. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: https://online.lexi.com/ . Accessed November 19, 2020.
- Vandvik PO, Lincoff AM, Gore JM, et al. Primary and Secondary Prevention of Cardiovascular Disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(4):e637-e668. doi:10.1378/chest.141.4.1129c.
- Kernan WN, Ovbiagele B, Black HR, et al. ). Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2017;45(7):2160-2236.
- Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. Journal of the American College of Cardiology. 2019;74(10):e177-e232. doi:10.1016/j.jacc.2019.03.015.
- McNeil JJ, Woods RL, Nelson MR, et al. Effect of Aspirin on Disability-free Survival in the Healthy Elderly . The New England Journal of Medicine . 2018;379(16):1499-1508.
- McNeil JJ, Nelson MR, Woods RL, et al. Effect of Aspirin on All-Cause Mortality in the Healthy Elderly . The New England Journal of Medicine . 2018;379(16):1519-1528.
- McNeil JJ, Wolfe R, Woods RL, et al. Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly . The New England Journal of Medicine . 2018;379(16):1509-1518.
- Guirguis-Blake JM, Evans CV, Senger CA, O’Connor EA, Whitlock EP. Aspirin for the primary prevention of Cardiovascular events: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2016; 164: 804-13.