Aspirin for the Primary Prevention of Cardiovascular Disease

• Aspirin protects against atherothrombosis while increasing the risk of major bleeding. 

• Current Studies
  • The ARRIVE study
    • Daily low dose aspirin (100 mg) did not reduce the long-term risk for cardiovascular or cerebrovascular events in more than 12,000 adults aged ≥ 55 years considered to be at a moderate risk of CVD.
    • stroke incidence did not differ significantly between treatment and placebo groups, 
    • rates of gastrointestinal bleeding and other minor bleeding were increased with aspirin.
  • The ASPREE study
    • low dose aspirin for primary prevention in 19,114 patients aged ≥ 70 years also did not reduce rates of all cardiovascular events, while significantly increasing the risk of major haemorrhage

NOTE: Diabetes mellitus is associated with a substantially increased CVD risk, meaning patients are generally excluded from primary prevention trials.

• the ASCEND study
  • over 15,000 adults aged ≥ 40 years with any type of diabetes and no prior history of cardiovascular events were randomly assigned low dose aspirin or placebo.
  • Aspirin reduced serious cardiovascular events by 12% (8.5% versus 9.6%; p=0.01), 
  • Major bleeding events increased by 29% (3.2% versus 4.1%; p=0.003)
  • Absolute benefits were outweighed by the added risk of bleeding in patients with diabetes.

In Australia 

• Currently no guidelines recommended in Australian guidelines
• clinical judgement is recommended in making decisions for aspirin use
• Further trials are currently underway to more comprehensively understand the risks and benefits of aspirin in primary CVD and cancer prevention

(https://www.racgp.org.au/clinical-resources/clinical-guidelines/key-racgp-guidelines/view-all-racgp-guidelines/national-guide/chapter-11-cardiovascular-disease-prevention)

In USA

• The US Preventive Services Task Force makes a level IB recommendation for the use of aspirin in people
  • aged 50–59 years + moderate to high CVD risk 
  • for the primary prevention of CVD and colon cancer
  • if there is no increased risk of bleeding.

New Zealand: 

• Aspirin is not recommended in people aged ≥ 70 years without a history of CVD
  • as the risk of major haemorrhage outweighs any potential benefits in this age group
• Consider the use of aspirin for primary prevention in people 
  • aged < 70 years
  • ≥ 15% five-year CVD risk
  • The benefits of aspirin may outweigh the increased risk of bleeding for primary CVD prevention in patients aged under 70 years with a ≥ 15% five-year CVD risk
  • potential benefit (reduction in non-fatal myocardial infarction and possible small net years gained) and bleeding risk must be carefully assessed and discussed during shared decision-making
• existing disease (secondary prevention)
  • existing CVD/documented coronary disease
  • carotid disease (plaque on ultrasound)
  • high coronary calcium score on CT scan (> 400)

considered to equate to high risk (>15%) and aspirin is recommended.

Age	Five-year CVD risk level		Recommendation for primary prevention of CVD	Recommendation for secondary prevention of CVD
	New CVD risk level (based on NZ Primary Prev eqn)	Old CVD risk level (based on Framingham eqns)
< 70 years	< 5%	< 10%	Aspirin is not recommended Intervention with lipid-lowering or blood pressure-lowering medicines has little benefit	Aspirin is recommended† **Provide lifestyle advice and pharmacotherapy for modifiable risk factors
	5–15%	10–20%	Aspirin is not recommended Discuss the benefits of lipid-lowering or blood pressure-lowering medicines
	≥ 15%	≥ 20%	Consider aspirin Lipid-lowering or blood pressure-lowering medicines are strongly recommended
≥ 70 years	All levels	All levels	Aspirin is not recommended
Asymptomatic carotid disease Asymptomatic coronary disease or plaque	Consider aspirin Lipid-lowering or blood pressure-lowering medicines are strongly recommended

Aspirin contraindications

• Active peptic ulceration, uncontrolled blood pressure and other major bleeding risks (including most people receiving an anticoagulant)
• Aspirin hypersensitivity/intolerance
• Severe hepatic or renal impairment
• all patients older than 70 years should not receive aspirin if they do not have a history of CVD, meaning de-prescribing should be considered. This recommendation is reinforced by the recent ASPREE study