Ohio Society of Health-System PharmacY

Author: Mason Fowler, PharmD Candidate 2020, Northeast Ohio Medical University College of Pharmacy (NEOMED); Cynthia King, PharmD, BCACP, CACP, MetroHealth System and NEOMED

Low-dose aspirin (LDA) has been considered a mainstay in the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD).¹ Recent data calls into question the appropriateness of LDA therapy for the nearly 30% of Americans age 40 years and older without a history of ASCVD taking a daily aspirin. The US Preventative Services Task Force in 2016 recommended LDA for adults 50-59 years with an ASCVD risk of at least 10% who are willing to take aspirin for at least 10 years and do not have an increased bleed risk.  Adults aged 60-69 years who have similar ASCVD risks are likely at increased risk of bleeding and may experience less benefit. ² Use of LDA for secondary prevention of ASCVD remains well established; however, the net benefit of aspirin for primary prevention is being questioned. 

Recent trials have focused on LDA therapy and the benefit for primary prevention of ASCVD.  The ASPREE trial was a double-blind, randomized, placebo-controlled trial designed to assess whether LDA prolongs life, or life free of dementia, or life free of significant, persistent physical disability in adults greater than 65 years of age. No difference was found in this composite endpoint, although the aspirin group did have a significant increase in major hemorrhage and all-cause mortality versus placebo.^3,4 The ARRIVE trial was a randomized, double-blind, placebo-controlled trial that examined the benefits of LDA in men at least 55 years old and women at least 60 years old with at least three cardiovascular (CV) risk factors and ASCVD risk score of 10-20% (moderate risk). The trial failed to show benefit of aspirin versus placebo in primary prevention of major CV event; however, less than 5% of all patients in the study had a major CV event.  A significant increase in gastrointestinal bleeding was seen in the aspirin group.⁵ Finally, the ASCEND study was a multicenter, double-blind, randomized, controlled trial to evaluated the benefit of aspirin therapy for primary prevention of major CV events in diabetic patients at least 40 years of age. This study found the group that received aspirin had a decreased number of major CV events compared to placebo. However, the aspirin group also had an increased risk of gastrointestinal bleed.⁶

A recent meta-analysis evaluating the CV and safety outcomes of LDA therapy for primary prevention of ASCVD included a total of 15 randomized controlled trials and 165,502 patients. Results showed the use of LDA versus placebo was not associated with changes in all-cause death, CV death, and non-CV death; a significant decrease in nonfatal myocardial infarction, transient ischemic attack, and ischemic stroke; and a significant increase in major bleeding, intracranial bleeding and major gastrointestinal bleeding. The efficacy analysis revealed the use of LDA resulted a in number needed to treat of 357 patients for myocardial infection, 400 patients for ischemic stroke, and 263 for major CV event. The safety analysis showed a number needed to harm of 222 patients for a major bleeding event, 385 patients for a gastrointestinal bleed, and 1000 patients for an intracranial bleed.  Based on this data, the net benefit of LDA for primary prevention of ASCVD is further called into question.⁷

The 2019 American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Primary Prevention of Cardiovascular Disease cautions providers routine use of LDA for primary prevention of ASCVD due to a lack of net benefit.  The ACC/AHA guidelines went on to further specify LDA should not be used for primary prevention in adults of any age who are at an increased risk of bleeding or those over the age of 70 years.  LDA may be considered in adults 40-70 years who have a high ASCVD risk but do not have an increased risk of bleeding.⁸

With new data on the use of LDA in patients for primary prevention of cardiovascular disease, healthcare providers need to closely evaluate whether LDA therapy is still appropriate for each patient. This will likely result in the deprescribing of aspirin therapy for many of our patients, especially in those 70 years and older or those at an increased bleed risk.  As the use of LDA has long been a corner stone in the primary prevention of ASCVD, pharmacists have the opportunity to provide education and reinforcement with our patients and other healthcare professionals regarding this major change in practice.

References

• 1. Baigent C, Blackwell L, Collins R, et al.; Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vas­cular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009; 373(9678): 1849-1860.
• 2. Bibbins-Domingo K; U.S. 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.
• 3. 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.
• 4. 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.
• 5. Gaziano JM, Brotons C, Coppolecchia, et al. 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. The Lancet. 2018; 392:1036-1046.
• 6. Bowman L, Mafham M, Stevens W, et al. ASCEND: A study of cardiovascular events in diabetes: characteristics of a randomized trial of aspirin and of omega-3 fatty acid supplementation in 15,480 people with diabetes. American Heart Journal. 2018;198:135–144. doi:10.1016/j.ahj.2017.12.006
• 7. Abdelaziz HK, Saad M, Pathineni NVK, et al. Aspirin for primary prevent of cardiovascular events. JACC. 2019;73(23). Doi:10.1016/j.jacc.2019.03.501
• 8. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology; 17 March 2019.