Definition and therapeutic rationale
Aspirin, or acetylsalicylic acid, is an antiplatelet drug that irreversibly inhibits cyclooxygenase and thereby suppresses thromboxane A2 synthesis. Thromboxane A2 promotes vasoconstriction and platelet aggregation. Because aspirin affects only one pathway of platelet activation, its antiplatelet effect is relatively limited compared with agents that inhibit other platelet pathways.
The distinction between primary and secondary prevention is fundamental:
Primary prevention refers to individuals without established atherosclerotic cardiovascular disease (ASCVD), coronary artery disease, cerebrovascular disease, or peripheral artery disease.
Secondary prevention concerns patients with established vascular disease, in whom aspirin has a substantially more favourable benefit–risk profile.
Aspirin is not a general-purpose cardiovascular preventive treatment. In people without established ASCVD, its potential reduction in non-fatal myocardial infarction and ischaemic stroke must be weighed against clinically important gastrointestinal and intracranial bleeding.
Evidence in primary prevention
Cardiovascular outcomes
Contemporary primary-prevention studies and meta-analyses show that aspirin can reduce non-fatal cardiovascular events, but does not reduce cardiovascular or all-cause mortality.
Reported relative effects include:
Approximately 11% reduction in cardiovascular events in a meta-analysis of primary-prevention trials involving individuals with an estimated 10-year cardiovascular risk of 10%.
Approximately 12% reduction in non-fatal myocardial infarction with low-dose aspirin.
Approximately 12% reduction in non-fatal ischaemic stroke in trials specifically evaluating this outcome.
No demonstrated reduction in cardiovascular or all-cause mortality.
Absolute benefit is modest. Across the updated systematic review, absolute reductions in major ASCVD events ranged from 0.8% to 2.5%. In people with a 10-year cardiovascular risk of approximately 10%, the number of cardiovascular events prevented was similar to the number of major bleeding events caused.
The evidence is not materially different by age or sex in the overall trial analyses. Some data from a study of healthy women suggested a reduction in ischaemic stroke, particularly among women with stroke risk factors, but this benefit was accompanied by increased serious gastrointestinal bleeding and a non-significant increase in cerebral haemorrhage.
Bleeding outcomes
The principal harm of aspirin in primary prevention is bleeding, which may occur relatively soon after treatment is initiated. Reported increases include:
Approximately 43% increase in major bleeding in a meta-analysis of primary-prevention trials.
Approximately 58% increase in major gastrointestinal bleeding.
Approximately 31% increase in intracranial bleeding.
In another meta-analysis, major bleeding increased by approximately 50%, intracranial bleeding by approximately 32%, and major gastrointestinal bleeding by approximately 52%.
There was no significant increase in fatal bleeding in the cited analyses. Nevertheless, the clinical importance of non-fatal gastrointestinal and intracranial haemorrhage is substantial, particularly because the absolute cardiovascular benefit is small in many primary-prevention populations.
Bleeding risk is especially relevant in older adults. Factors associated with increased gastrointestinal bleeding include:
Older age, with risk increasing particularly after 70 years
Male sex
Previous upper gastrointestinal disease
Hepatic or renal disease
Multiple cardiovascular risk factors
Concomitant nonsteroidal anti-inflammatory drugs
Corticosteroid therapy
Other antiplatelet or antithrombotic drugs
Selective serotonin reuptake inhibitors
Patient selection
Aspirin should not be prescribed routinely to individuals without established ASCVD. Selection requires simultaneous consideration of:
Estimated cardiovascular risk
Baseline bleeding risk
Age
Diabetes status
Current preventive treatment, particularly statin therapy
Patient preferences after discussion of likely absolute benefits and harms
The benefit–risk balance is less favourable in the contemporary prevention setting because statin therapy and other risk-factor interventions reduce baseline cardiovascular risk, whereas aspirin-associated bleeding risk persists.
Current recommendations
General primary prevention
European guidance has traditionally recommended against aspirin for primary prevention. More recent European recommendations allow consideration of low-dose aspirin in selected individuals with diabetes who have high or very high cardiovascular risk, provided bleeding risk is not high. For apparently healthy adults younger than 70 years with high or very high cardiovascular risk, decisions should be individualized.
The general principle is:
Aspirin may be considered only when cardiovascular risk is sufficiently high and bleeding risk is sufficiently low that the anticipated ischaemic benefit is judged to outweigh the haemorrhagic harm.
Routine use in low- or moderate-risk individuals is not recommended.
American recommendations
The 2019 AHA/ACC recommendations state that low-dose aspirin might be considered for primary prevention in adults aged 40–70 years who are at increased cardiovascular risk and are not at increased bleeding risk. Aspirin is not recommended for primary prevention in adults at increased bleeding risk.
The 2022 US Preventive Services Task Force recommendations are more restrictive:
Adults aged 40–59 years with a predicted 10-year ASCVD risk of at least 10%: the decision should be individualized; treatment represents a Grade C recommendation.
Adults aged 60 years or older: initiation of aspirin for primary prevention is not recommended; this represents a Grade D recommendation.
For adults with diabetes, the American Diabetes Association, AHA, and ESC recommend daily aspirin for secondary prevention, but do not recommend routine primary-prevention use. Low-dose aspirin may be considered in selected patients with diabetes who have increased or exceptionally high ASCVD risk, particularly when bleeding risk is low and the decision follows comprehensive shared decision-making. It is generally not favoured in older adults with diabetes.
Stroke prevention
Aspirin is no longer recommended for primary prevention of ischaemic stroke in people at low or medium cardiovascular risk. Although aspirin reduces ischaemic cardiovascular events, this benefit is counterbalanced by haemorrhagic events, including haemorrhagic stroke, and there is no net improvement in all-cause mortality.
In women, aspirin may be considered only in selected circumstances when individual stroke risk is judged to exceed bleeding risk. Evidence does not support routine antiplatelet therapy solely because diabetes is present in the absence of other major cardiovascular risk factors.
Diabetes without established ASCVD
Daily aspirin is not routinely indicated in diabetes without established ASCVD. It may be considered when ASCVD risk is very high or exceptionally high and bleeding risk is low. The decision should be individualized, because the reduction in ischaemic events is accompanied by a significant increase in major bleeding.
Lifestyle measures and control of modifiable risk factors remain the foundation of prevention in diabetes. These include smoking abstinence, at least 150 minutes of aerobic activity weekly, weight control, a healthy diet, blood-pressure management, and LDL-cholesterol reduction. Preventive pharmacotherapy, particularly statin treatment when indicated, does not carry the bleeding complication associated with aspirin.
Peripheral artery disease
Aspirin is not recommended systematically for asymptomatic peripheral artery disease without clinically relevant ASCVD. In asymptomatic peripheral artery disease with diabetes, aspirin at 75–100 mg may be considered in the absence of contraindications, although this is a selective rather than routine strategy.
Dose and practical prescribing
When aspirin is selected for primary prevention, the source material supports the use of low-dose aspirin, generally within the range of 75–100 mg once daily. Other guideline statements describe a daily dose of 75–162 mg, but the long-term preventive evidence indicates that doses of 75–100 mg appear as effective as higher doses.
Practical considerations include:
Avoid routine initiation in older adults, particularly those aged 60 years or more under the 2022 US Preventive Services Task Force recommendation.
Avoid treatment in patients with increased bleeding risk.
Review concomitant drugs that increase gastrointestinal or intracranial bleeding risk.
Reassess whether the patient remains an appropriate candidate as age, renal or hepatic disease, vascular risk, and concurrent medications change.
Use shared decision-making rather than treating a numerical risk threshold as an automatic indication.
Consider permanent discontinuation after individualized review in patients whose cardiovascular risk is low or moderate, particularly when bleeding risk is high.
The material does not provide a specific primary-prevention strategy for gastroprotection with proton-pump inhibitors. It notes that wider proton-pump inhibitor use might potentially amplify the benefit of aspirin in higher-risk primary-prevention patients, but this does not establish a general treatment recommendation.
Aspirin around non-cardiac surgery
For patients taking aspirin for primary prevention, the risk of peri-operative ischaemic events is low enough that aspirin can be withdrawn before non-cardiac surgery. Permanent post-operative discontinuation should be considered in patients with low or moderate ASCVD risk and/or high bleeding risk.
If the operation carries a particularly high bleeding risk, such as spinal surgery or certain neurosurgical or ophthalmological procedures, aspirin should be stopped for at least 7 days.
These considerations differ from secondary-prevention settings. In patients with established cardiovascular disease, aspirin has an established role in long-term prevention. In patients with previous percutaneous coronary intervention, low-dose aspirin should generally be continued peri-operatively unless bleeding risk is very high.
Special situations
Atrial fibrillation
Aspirin is not effective for preventing thromboembolic complications in atrial fibrillation. The reduction in stroke risk is variable and modest and is not greater than would be expected from reducing vascular stroke risk generally. Current atrial-fibrillation guidelines no longer recommend aspirin for stroke prevention. In patients with a low CHA2DS2-VASc score, the relevant options are an anticoagulant or no antithrombotic therapy, rather than aspirin.
Post-cardiac injury and post-pericardiotomy syndromes
Aspirin has a separate therapeutic role in post-cardiac injury syndromes and should not be conflated with primary cardiovascular prevention. For early post-myocardial-infarction pericarditis, a 5–7-day course of aspirin, combined with colchicine, is described as a reasonable approach. This indication is treatment of an inflammatory complication, not prevention in an otherwise disease-free individual.
Comparison with secondary prevention
The benefit–risk balance is substantially more favourable when ASCVD is already established. In patients with previous myocardial infarction, stroke, bypass surgery, angioplasty, peripheral artery disease, or angina, aspirin reduces serious cardiovascular events, non-fatal myocardial infarction, coronary events, and total stroke. The reduction in ischaemic events generally outweighs the increase in serious bleeding.
For chronic coronary syndrome, low-dose aspirin at 75–100 mg once daily is the traditional treatment for long-term secondary prevention, with clopidogrel 75 mg once daily as an alternative in appropriate patients.
After percutaneous coronary intervention, aspirin is usually continued indefinitely in patients without allergy, although lower dosing, such as 81 mg, may reduce gastrointestinal bleeding risk. In selected patients, aspirin may be stopped after a short period of dual antiplatelet therapy, with continuation of P2Y12-inhibitor monotherapy for 1–3 months after PCI in appropriate circumstances.
These secondary-prevention recommendations should not be extrapolated to patients without established ASCVD.
Follow-up and reassessment
No single follow-up schedule is specified in the source material. However, because primary-prevention aspirin has a narrow and highly individualized therapeutic margin, ongoing reassessment is essential. Review should include:
Whether the patient still meets the intended cardiovascular-risk profile
New gastrointestinal, renal, hepatic, or cerebrovascular disease
Development of factors that increase bleeding risk
Addition of nonsteroidal anti-inflammatory drugs, corticosteroids, antiplatelets, antithrombotics, or selective serotonin reuptake inhibitors
Advancing age, particularly beyond 60–70 years
Whether effective risk-factor treatment has reduced the residual cardiovascular benefit expected from aspirin
Patient understanding of the balance between prevention of non-fatal ischaemic events and major bleeding
The material does not define specific laboratory monitoring requirements for aspirin therapy. Clinical surveillance for bleeding and periodic reassessment of cardiovascular and haemorrhagic risk are therefore central to safe use.
Prognosis
Aspirin for primary prevention produces a modest reduction in non-fatal myocardial infarction and ischaemic stroke but no demonstrated mortality benefit. This benefit is offset by increased major gastrointestinal and intracranial bleeding, with the number of cardiovascular events prevented often similar to the number of major bleeding events caused in patients at approximately 10% 10-year cardiovascular risk.
Accordingly, prognosis is determined less by aspirin exposure alone than by the patient’s underlying ASCVD risk, bleeding susceptibility, and implementation of more effective preventive measures such as smoking abstinence, physical activity, weight control, healthy diet, blood-pressure treatment, and LDL-cholesterol reduction. In contemporary practice, aspirin has a limited, selective role in primary prevention and a much stronger role in secondary prevention.
