Effects of Changing Guidelines on Prescribing Aspirin for Primary Prevention of Cardiovascular Events

Jennifer Hissett, MD, Brittany Folks, MD, Letoynia Coombs, MS, William LeBlanc, PhD, and Wilson D. Pace, MD


J Am Board Fam Med. 2014;27(1):78-86. 

In This Article

Abstract and Introduction


Objective: The use of low-dose aspirin for primary prevention of cardiovascular events in patients at elevated risk for cardiovascular disease (CVD) is increasingly being questioned. Aspirin may not benefit this population and may increase the risk of major bleeding events. Data support aspirin use in patients with known CVD.

Methods: This is a secondary analysis of de-identified electronic health record (EHR) data from 131,050 individuals with known CVD or elevated risk for CVD as determined by diagnostic, demographic, and clinical data collected from 33 primary care practices in 11 different clinical organizations across 6 states. The percentage of the population of each cohort with aspirin recorded on their medication list, created through risk base analysis, was observed across 4 time periods.

Results: From 2007 to 2011, aspirin usage reflected in the EHR increased for the entire population and for each individual high-risk diagnosis. The percentage of the population initiating aspirin therapy for primary prevention within a year of diagnosis of CVD risk factors or CVD "equivalency" increased between 2007 and 2011. Among those with a new diagnosis of CVD, aspirin usage also steadily increased over the 4-year period, indicating no negative impact from new negative primary prevention studies.

Conclusions: Primary care clinicians have a central role in providing evidence-based preventive services and should integrate revised information into their practice to improve outcomes. Even with new evidence against the use of aspirin for primary prevention, it is difficult to change beliefs about the effectiveness and safety of aspirin, as reflected in the behavior of physicians and patients.


In 2002 the US Preventive Services Task Force began recommending low-dose aspirin as a primary prevention measure in patients at high risk of developing cardiovascular disease (CVD), defined as acute coronary syndrome or thrombotic cerebral vascular disease, when the benefit outweighs the risk.[1,2] This idea is increasingly being challenged. There is strong evidence that aspirin is beneficial for secondary prevention (prevention of overt symptoms or signs after the disease process has begun) of cardiovascular events.[3–5] However, no studies have shown the benefits of aspirin to outweigh the risks for those without CVD.[6–9] The US Food and Drug Administration has twice denied requests to approve aspirin for the primary prevention of cardiovascular events (which include both cardiac and cerebral events) in any population because of a lack of evidence supporting its efficacy.[10] Furthermore, research in patients with CVD risk equivalents (diabetes, chronic kidney disease, peripheral vascular disease) has demonstrated that the benefit of low-dose aspirin does not outweigh the harm.[11–15]

Multiple studies and meta-analyses indicate that there is no specific population in which the benefits of low-dose aspirin therapy for primary prevention exceed the risks. The Dialysis Outcomes and Practice Patterns Study (DOPPS), an observational investigation of aspirin use and cardiovascular morbidity and mortality among 28,320 patients receiving hemodialysis, found that among all patients with chronic kidney disease both with and without CVD, aspirin was associated with a decreased risk of thrombotic stroke but an increased risk of myocardial infarction and cardiac events.[11] The inclusion of patients with known CVD make a positive finding of stroke difficult to interpret.

The Prevention of Progression of Arterial Disease and Diabetes (POPADAD) trial examined the effects of aspirin and antioxidants, alone or in combination, among 1276 patients >40 years old with diabetes and asymptomatic peripheral artery disease in the absence of CVD. After 8 years of follow-up, the investigators found no reduction in the incidence of myocardial infarction, stroke, or deaths from CVD.[12] In the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, 2539 patients with type 2 diabetes were followed for 4 years. Low-dose aspirin did not reduce the risk of cardiovascular events and may have contributed to major gastrointestinal bleeds.[13]

In 2009, the Antithrombotic Trialists' Collaboration (ATTC) published a meta-analysis of 6 primary prevention trials (including 95,000 subjects with low overall average risk) and 16 secondary prevention trials (including 17,000 subjects with high overall average risk) comparing aspirin use with control. While they noted a decrease in nonfatal myocardial infarction among those taking aspirin for primary prevention, they also observed an increase in major bleeding events (both intracranial and gastrointestinal). They concluded that the risk of bleeding among those taking aspirin for primary prevention was increased by risk factors for coronary disease, and therefore guidelines recommending aspirin use for anyone with moderate to high risk of CVD should be reconsidered.[14]

A 2010 trial, Aspirin for Asymptomatic Atherosclerosis (AAA), addressed whether those without CVD but with a low Ankle-Brachial Index score would benefit from low-dose aspirin therapy. The investigators studied 3350 subjects with a low Ankle-Brachial Index score in the absence of CVD who were randomly assigned to receive either enteric-coated aspirin or placebo and followed for 8 years. There was no significant difference in thrombotic vascular events between the 2 groups. However, investigators found that the risk of a major bleeding event requiring hospitalization was higher among those taking aspirin.[15]

In 2010, the American Diabetes Association (ADA) and the American Heart Association (AHA)/American College of Cardiology changed their guidelines concerning the use of aspirin for primary prevention. The ADA previously recommended daily low-dose aspirin for all patients older than age 40, with diabetes, and with at least one other risk factor, such as hypertension.[16–18] The ADA recommendation now asserts that low-dose aspirin (75–162 mg/day) be considered for primary prevention of CVD for patients with diabetes with a >10% 10-year risk of CVD when the benefits outweigh the risks. This would include men >50 and women >60 years old who have diabetes and one other risk factor such as hypertension, smoking, dyslipidemia, or proteinuria. But, as outlined above, studies have not elucidated a single population in which the benefits of primary prevention exceed the risks.[19]

Primary care physicians (PCPs) have a central role in providing evidence-based preventive services and should incorporate revised information into their practice to improve patient outcomes. However, it is unknown how quickly PCPs are accepting new evidence about the lack of benefit of aspirin for primary prevention. Given the inclusion of the use of aspirin for primary prevention in national quality metrics and various pay-for-performance programs, it may be difficult to change the behavior of PCPs and patients. We initiated an investigation to determine whether recently published studies,[11–13,15] meta-analyses,[14] and changing guidelines[2,16–18] had an effect on aspirin prescribing practices of PCPs who are members of a national electronic practice-based research network, the Electronic Quality Improvement and Research Network (eNQUIRENet).