Introduction
Aspirin is an old drug with established use in the treatment of pain, inflammation and fever, and it is increasingly used for the prevention of cardiovascular disease (CVD).1 Based on prior work that elucidated the antiplatelet and antithrombotic effects of aspirin and the underlying processes that promote atherosclerotic plaque rupture, it is not surprising that this drug has become a cornerstone in the immediate therapies used in managing patients with acute coronary syndromes, as well as a measure for secondary prevention.2 The benefit of using antiplatelet medications such as aspirin for secondary prevention of atherosclerotic CVD has been widely accepted in clinical practice.3 In addition, the use of aspirin for primary prevention has also been incorporated into clinical practice over the last several decades. Still, more recent studies suggest that the risks and benefits of primary prevention should be more closely investigated.3
The clinical use of aspirin for the primary prevention of CVD was of particular interest in the late 1990s and early 2000s. The Physicians’ Health Study in 1989 found that aspirin 325 mg taken every other day reduced the risk of first myocardial infarction (MI) by 44% in healthy male patients aged 50 and older.4 Investigators found an increased risk of haemorrhagic stroke, though this was not statistically significant.4 Subsequent studies investigated the use of aspirin in reducing CVD when combined with anticoagulants, antihypertensives and vitamin E.5 In the late 1990s, the Thrombosis Prevention Trial evaluated the efficacy of aspirin 75 mg daily and low-dose warfarin in reducing the risk of ischaemic heart disease in high-risk patients. For aspirin-containing regimens (aspirin plus warfarin or aspirin alone), there was a 20% reduction in total fatal and non-fatal MIs. Notably, intermediate bleeding, namely haematuria, occurred more often in the warfarin plus aspirin group.6 The authors of the Hypertension Optimal Treatment Trial aimed to determine if low-dose aspirin combined with treatment and lowering diastolic blood pressure reduced the risk of major cardiovascular events. Major cardiovascular events were reduced by 15%, with a 36% reduction in fatal and non-fatal MI in patients with hypertension. There were non-significant decreases in cardiovascular mortality (5%) and overall mortality (7%). Fatal bleeding was similar across groups, but minor bleeding was more frequent in those taking aspirin.7 Similar results were seen with the Primary Prevention Project in 2001, which evaluated using aspirin in combination with vitamin E in patients aged 65 or older with hypertension, hypercholesterolaemia, diabetes, and a family history of premature cardiovascular events.8
In 2002, the United States Preventive Services Task Force (USPSTF) recommended the consideration of aspirin chemoprevention for patients at high risk for CVD, specifically men aged 40 years and older, postmenopausal women and younger patients with risk factors such as hypertension, diabetes and tobacco use.9 The American Heart Association (AHA) supported this recommendation but specifically recommended aspirin 75–160 mg daily in patients with a 10-year cardiovascular risk of at least 10%.10 Similarly, the 2003 update to the Standards of Medical Care for Patients with Diabetes Mellitus recommended aspirin therapy for all adult patients with diabetes and macrovascular disease, with consideration for patients aged 40 years and older with diabetes and one other cardiovascular risk factor.11
Results from the Women’s Health Study in 2005 led to an update to the AHA guideline 2007 that recommended aspirin therapy for high-risk women aged 65 and older.12 In 2009, the Antithrombotic Trialists’ Collaboration (ATT) completed a meta-analysis of six primary prevention studies evaluating aspirin in patients without diabetes with no history of occlusive disease who had been taking aspirin for at least 2 years. This meta-analysis demonstrated a 12% proportional reduction in major cardiovascular events, particularly non-fatal MI.13 These findings fueled further updates to USPSTF and AHA recommendations and the development of guideline recommendations from the American College of Chest Physicians. The 2016 USPSTF update took a more detailed approach, outlining recommendations for specific age groups based on the calculated 10-year CVD risk. Low-dose aspirin was recommended for adults aged 50–59 with a CVD risk of at least 10%. For adults aged 60–69 with a CVD risk of at least 10%, clinicians were encouraged to assess risk factors to make an informed decision about aspirin use.14–16 These guidelines were widely followed in clinical practice until 2018, following the publication of the Aspirin to Reduce Risk of Initial Vascular Events (ARRIVE), A Study of Cardiovascular Events in Diabetes (ASCEND) and Aspirin in Reducing Events in the Elderly (ASPREE) studies.17–19
The ARRIVE study was conducted in seven countries and assessed the efficacy of aspirin 100 mg daily in reducing the risk of major CV events for patients at moderate risk, defined as the presence of three or more cardiovascular risk factors in men aged 55 or older and women aged 60 or older. The authors found no significant difference in a composite endpoint of MI, stroke, CV death, unstable angina or transient ischemic attacks (TIA) but did find significantly more gastrointestinal bleeding events in the aspirin group.17 The ASCEND study evaluated patients with diabetes and included both high-risk and low-risk patient groups. Findings from the ASCEND study demonstrated a reduction in CV events but more frequent bleeding events.18 Lastly, the ASPREE study investigated the utility of aspirin in prolonging the lives of healthy community-dwelling older adults with no history of vascular disease. There was no difference in a composite endpoint of death, the onset of dementia and persistent physical disability, and the study was terminated early. Notably, this population had an increased risk of all-cause mortality, primarily cancer-related death. Though many types of cancer were observed, there was a higher rate of death from colorectal cancer.19
In 2019, the American College of Cardiology and the American Heart Association released updated primary prevention guidelines recommending that providers carefully assess atherosclerotic CVD risk and weigh this against bleeding risk before prescribing aspirin for primary prevention. Furthermore, these guidelines explicitly recommend against low-dose aspirin use for adults aged 70 and older.20 Though not published at this pilot study initiation, the USPSTF published a draft recommendation in October 2021 encouraging providers to avoid initiating low-dose aspirin for primary CV prevention in patients 60 years and older. In April 2022, the USPSTF published its final recommendations. For adults 40–59 with an ASCVD risk of 10% or greater, aspirin use for primary prevention should be made on a case-by-case basis. For adults aged 60 years and older, aspirin should not be initiated for primary prevention of CVD. Based on the supporting evidence used to generate these recommendations, the USPSTF also highlights that while the benefit of aspirin use is cumulative with time, the net benefit becomes smaller with age due to the increased risk of bleeding and suggests that it may be reasonable to discontinue aspirin at age 75 years or older. The Task Force does highlight the need for long-term data assessing the effects of low-dose aspirin on bleeding risk and colorectal cancer risk and mortality.21
As more data has become available, the benefits, risks and clinical recommendations for using aspirin in primary prevention have become less clear, and the decision to prescribe aspirin has become more individualised. Furthermore, no guidance has been provided on how to best manage patients who were previously prescribed aspirin for primary prevention per previous clinical guidelines. Often, this decision is left to primary care providers, who are in the best position to coordinate complex care for patients and comprehensively manage medications. In light of recent evidence and updated clinical recommendations regarding the safe and appropriate use of aspirin for primary prevention, primary care practices need to develop methods of identifying patients who may be taking aspirin unnecessarily. It is also essential to understand how recent studies and updated recommendations are interpreted by providers and translated into clinical practice.
The objectives of this study were to (1) develop an electronic medical record (EMR)-based systematic method for identifying patients aged 70 and older taking aspirin for primary prevention, (2) provide patient and provider education about updates to recommendations for aspirin use in primary prevention and (3) evaluate the impact of the intervention on aspirin use. In addition, the results of this study provide valuable information for other primary care practices looking to develop methods of identifying patients who may benefit from an assessment of the safety of aspirin use.