Primary and Secondary Prevention of Cardiovascular Disease: Aspirin 81 mg versus Aspirin 325 mg

As seen in the Consultant Connection July 2013 Issue
Lindsay Fleegle
Ohio Northern University
PharmD Candidate May 2014

Currently, cardiovascular disease is the number one cause of morbidity and mortality in the world. The disruption of an atherosclerotic plaque can increase platelet aggregation and eventually form a blood clot that can cause a cardiovascular event, for example a myocardial infarction or a stroke. A drug with anti-platelet effects, such as aspirin, has a substantial impact on morbidity and mortality in patients with cardiovascular disease.
Aspirin is commonly used for primary and secondary prevention of cardiovascular disease. However, there is uncertainty as to whether aspirin 81 mg (low-dose) or aspirin 325 mg should be used. Aspirin is both an anti-platelet and anti-inflammatory agent due to its mechanism of action. It exerts its effect by inhibiting COX1, an enzyme involved in platelet function, and COX2, an enzyme involved in the inflammatory response. As a result of COX1 inhibition, a side effect of aspirin is gastrointestinal mucosal damage, including ulcers and bleeding. Symptoms of damage consist of gastrointestinal distress and blood in the stool. Gastrointestinal damage is a dose related side effect which can lead to the discontinuation of the medication. Therefore, in order to minimize the bleeding risk associated with this drug and effectively provide prophylaxis from a cardiovascular event, a once daily low-dose aspirin can be given because it is enough to inhibit COX1 dependent platelet function.
  For primary prevention of cardiovascular disease, the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (CHEST) recommend low-dose aspirin 75-100 mg daily over no aspirin therapy for persons aged 50 years or older without symptomatic cardiovascular disease. Still, the risk versus benefit of long-term aspirin therapy needs to be considered for each individual patient. For individuals at a high risk of future cardiac events, due to the presence of significant risk factors such as hypertension, diabetes, hyperlipidemia, tobacco use, physical inactivity, and obesity, then prophylactic aspirin should be considered, but weighed against the risk of potential complications. On the other hand, the risk of gastrointestinal side effects may outweigh the benefits of aspirin therapy in low risk patients.
The advantage of long-term aspirin therapy is more pronounced in secondary prevention of cardiovascular disease. The CHEST guidelines recommend long-term single anti-platelet therapy with aspirin 75-100 mg daily or clopidogrel 75 mg daily over no anti-platelet therapy for patients with established coronary artery disease. The guidelines also suggest single therapy over dual anti-platelet therapy with aspirin plus clopidogrel. Coronary artery disease is defined as patients one year post-acute coronary syndrome, with prior revascularization, coronary stenoses greater than fifty percent by coronary angiogram, and/or evidence for cardiac ischemia on diagnostic testing.
Overall, the CHEST guidelines recommend low-dose aspirin for both primary and secondary prevention of cardiovascular disease. Low-dose aspirin is an anti-platelet agent that has been shown to effectively decrease fatal and nonfatal cardiovascular events, mainly in secondary prevention. However, before any patient is started on low-dose aspirin, a risk versus benefit analysis should be performed, especially in primary prevention.

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