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Antiplatelet Therapy With Aspirin: What Dose in Primary and Secondary Prevention?


Use of aspirin in primary prevention of cardiovascular disease must be based on individual risk-benefit analysis and is not appropriate for patients at low risk.

More than 50 million US adults take aspirin regularly for long-term prevention of cardiovascular disease (CVD) and mortality, typically 81 or 325 mg/d. But while aspirin is still the most widely studied antiplatelet drug in the world, controversy remains regarding the most appropriate long-term daily dose and whether the drug has a role in primary prevention.

A meta-analysis published earlier this year in the Archives of Internal Medicine1 is the latest in a series of inquiries that compare CVD risk reduction against elevated risk of bleeding to assess the net benefit of aspirin prophylaxis in primary and secondary prevention.2-5 The results corroborate existing data that suggest the principal cardiovascular effect of aspirin in primary prevention is on nonfatal MI with no real benefit with regard to fatal MI, stroke, or CVD death. Even these benefits are considerably offset by an elevated risk of bleeding.

• What does this analysis add to our understanding of the interplay of aspirin dosing, efficacy, and safety?
• How do risks and benefits of aspirin prophylaxis differ in primary and secondary prevention?
• How should primary care clinicians approach the aspirin versus statin question with patients who are at risk, but low risk, for CVD?

Here to put this issue into perspective are Drs Christopher Cannon and Payal Kohli. Dr Cannon, a senior investigator with the TIMI Study Group, is Editor-in-Chief of Cardiosource Science and Quality. He is also Professor of Medicine at Harvard Medical School and Associate Physician in the Cardiovascular Division of Brigham and Women’s Hospital in Boston. Dr Kohli graduated from Harvard Medical School, completed her internal medicine training in Boston, and is currently a fellow in cardiovascular medicine at the University of California San Francisco.

Antiplatelet Therapy with Aspirin

Take-Home Points

1. Aspirin in primary prevention:

a. In high-risk patients (Framingham Risk Score ≥10%) and anyone with established coronary disease, aspirin 81 mg/d should be used
b. In borderline-risk patients (Framingham Risk Score = 5% to 10%), decisions should be individually tailored and aspirin should be used if the benefit outweighs the risk of bleeding
c. In low-risk patients (Framingham Risk Score <5%), using aspirin for primary prevention can actually result in more bleeding than benefit. These very low-risk patients should be taken off aspirin and lifestyle modification should be encouraged instead.

2. Aspirin in secondary prevention: In anyone with established coronary disease (included those who have been instrumented), 81 mg/d of aspirin should be used instead of 325 mg/d.

3. Unlike statins, aspirin is not disease-modifying and exerts its beneficial effect via antithrombotic mechanisms on a ruptured plaque. Therefore, it is less effective in patients who may not have significant plaque burden.


References1. Seshasai SRK, Wijesuriya S, Sivakumaran R, et al. Effect of aspirin on vascular and nonvascular outcome: Meta-analysis of randomized controlled trials. Arch Intern Med. 2012;172:209-216.
2. Peters RJG, Mehta SR, Fox KAA, et al, for the CURE trial investigators. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: Observations from the clopidogrel in unstable angina to prevent recurrent events (CURE) study. Circulation. 2003;108:1682-1687.
3. Campbell CL, Smyth S, Montalescot G, Steinhubl SR. Aspirin dose for the prevention of cardiovascular disease: A systematic review. JAMA. 2007;297:2018-2024.
4. Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849-1860.
5. Mehta SR, Bassand JP, Chrolavicius S, et al. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med 2010;363:930-942.


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