The USPSTF April 2016 recommends low-dose aspirin to prevent cardiovascular disease and colorectal cancer in the following groups:

Grade B Adults age 50 to 59 years with a 10 year CVD risk of greater than 10% who are not at increased risk for bleeding, have a life expectancy of at least 10 years and are willing to take low-dose aspirin for at least 10 years.

Grade C Adults age 60 to 69 years with a 10 year CVD risk of greater than 10% should consider their individual risks versus benefits of long term low dose aspirin. Those who are not at risk of bleeding, have a life expectancy of at least 10 years and are willing to take low-dose aspirin for at least 10 years are more likely to benefit.

“Persons who place a higher value on the potential benefits than the potential harms may choose to initiate low-dose aspirin.”

The USPSTF state that there is insufficient current evidence to assess the balance of benefits versus harms of initiating aspirin for primary prevention of CVD and CRC in adults younger than 50 years or 70 years or older. (Grade I).

For more information see:

https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/aspirin-to-prevent-cardiovascular-disease-and-cancer

The USPSTF is currently commissioning an update to its guidance on aspirin and primary prevention. More information can be found at:

https://www.uspreventiveservicestaskforce.org/uspstf/draft-update-summary/aspirin-use-to-prevent-cardiovascular-disease-and-colorectal-cancer-preventive-medication

The American College of Cardiology (ACC) and American Heart Association (AHA) Guidelines on the primary prevention of cardiovascular disease (2019 ACC/AHA Guidelines on the primary Prevention of Cardiovascular Disease) states:

“Aspirin is well established for secondary prevention of [atherosclerotic cardiovascular disease] ASCVD and is widely recommended for this indication, but recent studies have shown that in the modern era, aspirin should not be used in the routine prevention of ASCVD due to lack of net benefit.”

In particular they state that aspirin should be avoided in the following groups:

• People with an increased risk of bleeding e.g. history of GI bleeding, bleeding from other sites, age> 70 years, thrombocytopenia, coagulopathy, chronic kidney disease and concurrent use of NSAIDS and anticoagulants.

AHA makes the following recommendations based on a meta-analysis of 3 recent trials:

• “Low-dose aspirin might be considered for primary prevention of ASCVD in select higher ASCVD adults aged 40-70 years who are not at increased bleeding risk
• Low-dose aspirin should not be administered on a routine basis for primary prevention of ASCVD among adults > 70 years.
• Low-dose aspirin should not be administered for primary prevention among adults at any age who are at increased bleeding risk.”

For further information see:

https://www.jacc.org/doi/pdf/10.1016/j.jacc.2019.03.010

The American Diabetes Association (ADA) (Cardiovascular disease and risk management: Standards of Medical Care in Diabetes-2020. Diabetes Care 2020; 43(suppl.1): S111-S134) state that for the case of primary CVD prevention;

‘Aspirin therapy (75-162mg/day) may be considered as a primary prevention strategy in those with diabetes who are at increased cardiovascular risk, after a comprehensive discussion with the patient on the benefits versus the comparable increased risk of bleeding.’

The ADA review clinical trial work including the Antithrombotic trialists’ collaboration, ASCEND, ARRIVE and ASPREE and conclude that aspirin appears to have a modest impact on decreasing ischemic vascular events especially where atherosclerotic cardio vascular disease (ASCVD) risk is higher. This however is tempered by its main side effect of increased gastrointestinal (GI) bleeding which may be as high as 5 per 1,000 per year in the real-world setting. Where ASCVD risk is more than 1% per year the number of ASCVD events that are averted are comparable to the number of GI bleeding events caused. The ADA however recognise that CVD events and GI bleeding events ‘do not have equal effects on long-term health’.

The ADA explain that men and women age 50 years or older with diabetes and one additional CVD risk factor such as family history of ASCVD, high blood pressure, high cholesterol, smoking, chronic kidney disease and who are not at increase bleeding risk e.g. older age, anaemia, renal disease, are most likely to benefit from using low-dose aspirin for the primary prevention of ASCVD. They also suggest that non-invasive imagining techniques could potentially help identify people for aspirin primary prevention therapy.

For more information see:

https://care.diabetesjournals.org/content/44/Supplement_1/S125

Secondary prevention of cardiovascular disease

The American College of Cardiology (ACC) and American Heart Association (AHA) Guidelines on the primary prevention of cardiovascular disease 2019 guidance states;

“Aspirin is well established for secondary prevention of [atherosclerotic cardiovascular disease] ASCVD and is widely recommended for this indication.”

The AHA/ASA stoke guidelines (Guidelines for Early Management of Patients With Acute Ischemic Stroke: 2019) state:

“Administration of aspirin is recommended in patients with AIS [acute ischemic stroke] within 24-48 hours after onset. For those treated with IV alteplase, aspirin administration is generally delayed until 24 hours later but might be considered in the presence of concomitant conditions for which such treatment given in the absence of IV altephase is known to provide substantial benefit or withholding such treatment is known to cause substantial risk.”

For further information see:

https://www.ahajournals.org/doi/epub/10.1161/STR.0000000000000211

The American Diabetes Association (ADA) (Cardiovascular disease and risk management: Standards of Medical Care in Diabetes-2020. Diabetes Care 2020; 43(suppl.1): S111-S134) recommends low-dose aspirin (75-162 mg/day) for secondary prevention in people with a history of cardiovascular disease (CVD). For those unable to take aspirin, clopidogrel (75mg/day) can be used. Dual antiplatelet therapy with low-dose aspirin and a P2Y12 inhibitor is recommended for at least a year after acute coronary syndrome therapy (ACS).

For more information see:

https://care.diabetesjournals.org/content/44/Supplement_1/S125

European guidelines

Primary prevention of cardiovascular disease

Key Message: “Antiplatelet therapy is not recommended in individuals free from CVD, due to the increased risk of major bleeding.” European Society of Cardiology (ESC) 2016

The 2016 European guidelines on CVD prevention review the evidence for antiplatelet therapy in individuals without CVD and conclude that current evidence does not support the use of aspirin in those without CVD due to the risk of a major bleed.

For more information see:

https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/CVD-Prevention-in-clinical-practice-European-Guidelines-on

The ESC 2019 guidelines on diabetes (DM), pre-diabetes, and cardiovascular disease state:

• “Patients with DM and symptomatic CVD should be treated no differently to patients without DM
• In patients with DM at moderate CV risk, aspirin for primary prevention is not recommended
• In patients with DM at high/very high CV risk, aspirin may be considered in primary prevention

For more information see:

https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Diabetes-Pre-Diabetes-and-Cardiovascular-Diseases-developed-with-the-EASD

In addition, the ESC 2019 diabetes guidelines identify the following gaps in the evidence relating to platelet use in people with diabetes:

• Type 1 diabetes and CVD prevention [in vivo platelet activation has been reported]
• Body mass and antiplatelet responsiveness especially in those with diabetes and obesity where higher dose strategies need investigation
• Are antithrombotic effects similar in pre-DM and DM?

The ESC does not recommend aspirin for healthy people over 70 following results of the ASPREE trial.

https://www.escardio.org/The-ESC/Press-Office/Press-releases/aspirin-should-not-be-recommended-for-healthy-people-over-70

The ESC state in a press release following results of ARRIVE that the benefits of aspirin in primary prevention remain unclear.

https://www.escardio.org/Congresses-&-Events/ESC-Congress/Congress-resources/Congress-news/benefit-of-aspirin-for-primary-prevention-of-cardiovascular-events-remains-unclear-arrive-trial-results

In another press release following the ASCEND trial the ESC state that the bleeds and benefits are balanced in people with diabetes using aspirin for primary CVD prevention and that no cancer benefit was found in this study.

https://www.escardio.org/The-ESC/Press-Office/Press-releases/bleeds-and-benefit-with-aspirin-balanced-in-patients-with-diabetes-and-no-effect-on-cancer

Secondary prevention of cardiovascular disease

The 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes recommended aspirin for CVD event prevention at a dose of 75-100 mg daily in patients with previous MI or revascularization. In addition, aspirin 75-100 mg daily can also be considered for people without a history of MI or revascularization but where there is evidence of coronary artery disease using imaging tests.

For further information see:

https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Chronic-Coronary-Syndromes

The 2016 European Guidelines for CVD prevention in clinical practice make the following recommendations for antiplatelet therapy (see table below). This is a based on a careful appraisal of risks versus benefits of aspirin or other antiplatelet therapy. The guidelines state that there is a gap in the evidence concerning new antiplatelet drugs in patients with stable coronary artery disease as well as a gap in the understanding about the use of new antiplatelet drugs used in combination with anticoagulation treatment.