Is aspirin (acetylsalicylic acid) indicated for primary prevention of cardiovascular events?

From the Guidelines

Aspirin is generally not recommended for primary prevention of cardiovascular disease in most individuals, as the risks of bleeding complications often outweigh the potential cardiovascular benefits. For primary prevention, the decision to use aspirin should be individualized and made after discussing potential benefits and harms with a healthcare provider, considering factors such as cardiovascular risk factors, bleeding risk, and age 1. Aspirin may be considered in select high-risk individuals aged 40-70 who have elevated cardiovascular risk factors but low bleeding risk, typically at doses of 81-100 mg daily. Specific groups who might benefit include those with multiple risk factors such as diabetes, hypertension, and hyperlipidemia, especially if their 10-year cardiovascular risk exceeds 10% 1.

Key Considerations

• The Antithrombotic Trialists’ Collaboration published an individual patient–level meta-analysis of the six large trials of aspirin for primary prevention in the general population, which found that aspirin reduced the risk of serious vascular events by 12% (relative risk 0.88 [95% CI 0.82–0.94]) 1.
• The ASCEND (A Study of Cardiovascular Events iN Diabetes) trial randomized 15,480 people with diabetes but no evident cardiovascular disease to aspirin 100 mg daily or placebo, and found a significant 12% reduction in the primary efficacy end point, but also a significant increase in major bleeding 1.
• For people >70 years of age (with or without diabetes), the balance appears to have greater risk than benefit, and aspirin is generally not recommended 1.

Mechanism and Risks

• Aspirin works by inhibiting platelet aggregation through irreversible inhibition of cyclooxygenase, reducing thrombus formation, but this same mechanism increases bleeding risk, particularly gastrointestinal and intracranial hemorrhage 1.
• Recent guidelines have shifted away from routine aspirin use for primary prevention as newer data suggests the harms may exceed benefits for many people, especially those over 70 years old and those with increased bleeding risk 1.

From the Research

Aspirin for Primary Prevention of Cardiovascular Events

• The use of aspirin for primary prevention of cardiovascular events has been a topic of controversy, with some studies showing modest benefit and others showing no benefit or even harm 2, 3, 4, 5.
• Early trials suggested that aspirin could reduce the risk of myocardial infarction and stroke in patients with no history of cardiovascular disease, but more recent trials have failed to show a significant benefit 4, 5.
• The 2021 review of evidence on the use of aspirin for primary prevention of cardiovascular disease found that aspirin had a neutral net benefit or even harm in patients with no overt cardiovascular disease 2.
• The 2010 review of aspirin for primary prevention of cardiovascular disease in patients with diabetes mellitus found that aspirin reduced the relative risk of myocardial infarction and stroke by about 10%, but also increased the risk of gastrointestinal bleeding 3.
• The 2016 review of aspirin for primary prevention of cardiovascular disease found that the role of aspirin in primary prevention was unclear, and that the exact reasons for the lack of efficacy in recent trials were unclear 4.
• The 2020 review of aspirin in primary and secondary prevention of cardiovascular disease found that the utility of aspirin therapy in patients without established cardiovascular disease was less clear, and that recent trials had demonstrated modest to no benefit in preventing cardiovascular events and mortality with aspirin use for primary prevention 5.
• The 2017 review of the use and misuse of aspirin in primary cardiovascular prevention found that the evaluation of the net clinical benefit of aspirin was an important point of debate, and that a cutoff level of global CV risk above which the net clinical benefit of aspirin becomes evident was needed 6.

Key Findings

• Aspirin may not be indicated for primary prevention of cardiovascular events in patients with no history of cardiovascular disease 2, 4, 5.
• Aspirin may be beneficial for primary prevention of cardiovascular events in patients with diabetes mellitus, but the benefit is modest and must be weighed against the increased risk of gastrointestinal bleeding 3.
• The use of aspirin for primary prevention of cardiovascular disease should be based on the level of global CV risk, with a suggested cutoff of 1 or more major CV events per 100 persons per year 6.