By: Jun Suh Hong, PharmD candidate c/o 2022
Aspirin belongs to a class of medications called nonsteroidal anti-inflammatory drugs (NSAIDS). Known by many for its analgesic and anti-inflammatory properties, as well as its association with gastrointestinal (GI) bleeding, aspirin plays an essential role in stroke prevention. As such, it has a crucial role in the lives of many living with cardiovascular conditions.1 As of October 2021, however, there has been a change in guidance regarding its use for prophylaxis.
The leading cause of death in the United States is heart disease. Approximately 659,000 people die annually from cardiovascular events including heart attacks, stroke, and coronary artery disease. Heart disease is an umbrella term that refers to several types of heart conditions including but not limited to arrhythmias and coronary artery disease, which affect blood flow to the heart. These conditions can increase the risk of a heart attack or stroke. Other risk factors for heart disease include high blood pressure, high cholesterol, diabetes, as well as lifestyle habits (unhealthy diet and physical inactivity).2
Aspirin is an irreversible cyclo-oxygenase (COX)-1 and COX-2 enzyme inhibitor. Unlike other NSAIDS, aspirin has a higher propensity for the COX-1 variant at a dose of <100mg/day which leads to decreased production of thromboxane A2. For reference, thromboxane is a type of eicosanoid similar to prostaglandins, that promotes platelet aggregation and vasoconstriction, resulting in clotting activity. COX-1 is also an enzyme responsible for producing some prostaglandins which are associated with GI protection. The COX-2 activity remains intact at low doses of aspirin, which still allows prostaglandin I2 to be produced. Prostaglandin I2 acts as a vasodilator and platelet inhibitor which aids in the anticlotting properties. By decreasing thromboxane and continuing prostaglandin I2 production, aspirin can reduce thrombosis and prevent cardiovascular events. However, in doing so, aspirin can also alter the GI mucosa protection through its inhibition on the COX-1 enzyme. This results in reduced production of protective GI prostaglandins, which predisposes patients to GI bleed.3
In 2016, the United States Preventive Services Task Force (USPSTF) announced a universal recommendation in support of initiating aspirin for the first time in high-risk patients 50-59 years old, as long as their risk of bleeding was low. Risk is based on the score calculated using the atherosclerotic cardiovascular disease (ASCVD) Risk Calculator, which measures the patient’s chances of having a cardiovascular event in the next 10 years. High risk (ASCVD score > 10%) adults 60 and older were recommended to consult their doctors prior to making a decision. However, as of October 2021, the USPSTF has retreated from their recommendation and is strongly discouraging anyone 60 years of age and older from starting a low-dose aspirin regimen, citing concerns of age-related heightened risk for life-threatening bleeding.1 High risk adults (>10%), between ages 40 to 59 years old, are now recommended to talk with their doctors and make a personal, individualized choice on whether to initiate a low-dose aspirin daily regimen.
This change in aspirin recommendations comes years after advice against its general use from several other medical organizations and federal agencies. In 2014, the FDA conducted a review of aspirin that concluded in discouraging its use for primary prevention of heart disease, noting the side effects related to bleeding. The FDA stated, “there are serious risks associated with the use of aspirin, including increased risk of bleeding in the stomach and brain, in situations where the benefit of aspirin for primary prevention has not been established”.4 In 2019, the American College of Cardiology and American Heart Association came together to narrowly recommend that low-dose aspirin might be considered for primary prevention of ASCVD in select high risk adults aged 40-70 years who are not at increased bleeding risk. They advised against the use of low-dose aspirin in patients >70 years old for primary prevention of ASCVD, with the goal to prevent further increased risk of bleeding.5
The call for change in recommendation of aspirin comes from mounting evidence in support of non-superiority. One such example is the Aspirin to Reduce Risk of Initial Vascular Events (ARRIVE) trial. This was a randomized, double-blind, multicentered, placebo-controlled study of more than 12,000 participants. The study population included men aged ≥55 years and women aged ≥60 years with a 10-year risk of major adverse cardiovascular events (MACE) who were randomized to take 100mg of Aspirin (81-100mg is considered low dose) or a placebo, in addition to antihypertensives and statins, for a period of 5 years. Over a median 60-month follow-up, there was no significant difference in efficacy between both groups in preventing MACE, with a recorded hazard ratio (HR) of 0.96 and a 95% confidence interval (CI) of 0.81–1.13 (p = 0.604). Similarly, the incidence of mortality rates were not significantly different. With respect to safety, GI bleeding events were more frequent in the aspirin groups than in the placebo groups (HR = 2.11, 95% CI = 1.36–3.28; p<0.001).6 The overall net balance of benefit to harm is non-superior, which is why the USPSTF has decided to revise their previous recommendations.
As pharmacists and aspiring clinicians, it is imperative that we stay abreast of these recommendation updates, so we can continue to provide the best care for our patients. Fortunately, aspirin is not the only therapeutic option for preventing heart disease. Patients should, as always, be encouraged to maintain a healthy diet, engage in physical activity where possible, and adhere to their medications regimens so they can manage any comorbidities (hypertension, hyperlipidemia, etc).
- Rabin R. Aspirin Use to Prevent 1st Heart Attack or Stroke Should Be Curtailed, U.S. Panel Says. New York Times. https://www.nytimes.com/2021/10/12/health/aspirin-heart-attack-stroke. html?auth= login-google.Published 10/12/2021. Accessed October 30, 2021
- Centers for Disease Control and Prevention. 2021. Heart Disease Facts | cdc.gov. https://www.cdc.gov/heartdisease/facts.htm. Accessed 20 October 2021.
- Guirguis-Blake, J., Evans, C., Senger, C., Rowland, M., O’Connor, E. and Whitlock, E., 2021. Introduction. Ncbi.nlm.nih.gov. https://www.ncbi.nlm.nih.gov/books/NBK321625/. Accessed 20 October 2021.
- U.S. Food and Drug Administration. 2021. Use of Aspirin for Primary Prevention of Heart Attack and Stroke. https://www.fda.gov/drugs/information-consumers-and-patients-drugs/use-aspirin-primary-prevention-heart-attack-and-stroke. Accessed 20 October 2021.
- American College of Cardiology. 2021. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease – American College of Cardiology. https://www.acc.org/latest-in-cardiology/ten-points-to-remember/2019/03/07/16/00/2019-acc-aha-guideline-on-primary-prevention-gl-prevention. Accessed 20 October 2021.
- Anatol J Cardiol. Aspirin for primary prevention of cardiovascular disease 2020 Feb; 23(2): 70–78. doi: 10.14744/AnatolJCardiol.2019.89916. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040875/. Published 2019 Dec 18 Accessed October 30, 2021