What randomized controlled trials support the use of low-dose Acetylsalicylic acid (Aspirin) for primary prevention of cardiovascular events?

From the Guidelines

Low-dose aspirin for primary prevention of cardiovascular events should be considered in adults aged 40-70 with a high cardiovascular risk and low bleeding risk, as evidenced by a patient-level meta-analysis of six large trials that found a 12% reduction in serious vascular events 1. The use of low-dose aspirin for primary prevention has been supported by several randomized controlled trials, including those that collectively enrolled over 95,000 participants, with almost 4,000 having diabetes 1.

• The trials found that aspirin reduced the risk of serious vascular events by 12% (relative risk 0.88 [95% CI 0.82–0.94]) 1.
• The largest reduction was for nonfatal MI, with little effect on CHD death or total stroke 1.
• However, the rate of major hemorrhage per 1,000 person-years was 8.6 events vs. 6.2 events, respectively (HR 1.38 [95% CI 1.18–1.62]; P < 0.001) 1. Key considerations for the use of aspirin in primary prevention include:
• Adults with diabetes and at least one additional major risk factor (family history of premature ASCVD, hypertension, dyslipidemia, smoking, or chronic kidney disease/albuminuria) who are not at increased risk of bleeding 1.
• Noninvasive imaging techniques such as coronary calcium scoring may help further tailor aspirin therapy, particularly in those at low risk 1.
• For patients over the age of 70 years, the balance appears to have greater risk than benefit, and aspirin is generally not recommended for primary prevention 1. Aspirin therapy for primary prevention should be carefully considered and may be considered in the context of shared decision-making, weighing the cardiovascular benefits with the increase in risk of bleeding 1.

From the Research

Randomized Controlled Trials for Primary Prevention of Cardiovascular Events with Low-Dose Aspirin

• The use of low-dose aspirin for primary prevention of cardiovascular events has been studied in several randomized controlled trials 2, 3.
• A systematic review and meta-analysis of 10 randomized clinical trials found that low-dose aspirin was associated with a significant reduction in major adverse cardiovascular events (MACE), myocardial infarction (MI), and ischemic stroke (IS) 2.
• However, the same study also found that aspirin increased the risk of major bleeding, intracranial hemorrhage, and gastrointestinal (GI) bleeding 2.
• Another systematic review and meta-analysis of 13 randomized clinical trials found that aspirin use was associated with significant reductions in the composite cardiovascular outcome, but also increased the risk of major bleeding events 3.
• The benefits and risks of aspirin use for primary prevention may vary depending on individual patient characteristics, such as cardiovascular risk and age 2, 3.

Subgroup Analyses and Individual Patient Characteristics

• Subgroup analyses have found that the benefits of aspirin may be greater in patients with high cardiovascular risk 2, 3.
• Patients with diabetes may also benefit from aspirin use, although the evidence is limited 4, 2.
• Age may also be an important factor, with patients aged ≤ 70 years potentially benefiting more from aspirin use than those aged > 70 years 2.
• The risk of bleeding may be higher in certain patient subgroups, such as those with a history of gastrointestinal bleeding 5.

Bleeding Risks and Cardiovascular Benefits

• The balance between the potential benefits and risks of aspirin use for primary prevention is critical 6, 4.
• The risk of bleeding associated with aspirin use must be carefully weighed against the potential cardiovascular benefits 2, 3.
• Individual patient characteristics and risk factors should be taken into account when deciding whether to use aspirin for primary prevention 2, 3.