Effective Aspirin Dose
Effective Aspirin Dose
Abstract & Commentary
By Michael H. Crawford, MD, Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer.
Synopsis: The majority of chronic stable coronary artery disease patients given 75 mg of EC aspirin daily have adequate inhibition of COX, but younger, heavier, and post MI patients may not.
Source: Maree AO, et al. Platelet response to low-dose enteric-coated aspirin in patients with stable cardiovascular disease. J Am Coll Cardiol. 2005;47:1258-1263.
Aspirin resistance is a concern for the long-term treatment of patients with cardiovascular disease. Maree and colleagues from Dublin, Ireland, tested the hypothesis that low-dose enteric-coated (EC) aspirin provides inadequate drug bioavailability and incomplete inhibition of platelet aggregation in 131 stable patients with atherosclerotic coronary artery disease who were taking 75 mg a day of EC aspirin. Serum thromboxane (TX) B2 was measured to assess cyclooxygenase (COX) activity. A subgroup also had arachidonic acid (AA) stimulated TX B2 production from platelet-rich plasma and platelet aggregation measured. If platelet aggregation was detected, the assay was repeated after adding aspirin to the platelet-rich plasma.
Forty-four percent of the patients had elevated TX B2 levels, which indicates a suboptimal response to aspirin. Patients with a suboptimal response to aspirin were more likely to exhibit platelet aggregation to AA (21% vs 3% of those with low TX B2 levels, P = .004). When platelet aggregation was shown with AA, it was always abolished by addition of aspirin in vitro. Patients who showed suboptimal aspirin responses were younger, heavier, and more likely to have had a previous myocardial infarction (MI) on multiple regression analysis. Maree et al concluded that the majority of chronic stable coronary artery disease patients given 75 mg of EC aspirin daily have adequate inhibition of COX, but younger, heavier, and post MI patients may not.
Commentary
Aspirin irreversibly inhibits COX and prevents the conversion of AA to TX, which is required for platelet aggregation. In healthy volunteers, 30-40 mg of aspirin will effectively cease platelet aggregation in vitro. In patients, studies have shown that such inhibition is easily obtained with 75-150 mg of plain aspirin, because the average bioavailability of aspirin is about 50%. This study tested the effect of EC aspirin in patients, and found a high level of inadequate responses (44%). The reason for this suboptimal response is not known, but enteric coating may inhibit absorption of aspirin or hasten its breakdown. This is supported by the association of a suboptimal response with heavier and younger individuals. More importantly, those with a previous MI were also more likely not to respond to 75 mg of EC aspirin for reasons that are unclear. However, these data suggest that patients with chronic stable coronary atherosclerosis, especially if they are post MI, should receive at least 150-162 mg of EC aspirin or plain aspirin if they can tolerate it. Low-dose (75-81 mg) aspirin is probably adequate for primary prevention, especially if plain aspirin is used. The practice of using lower doses of aspirin in the elderly is supported by this study, since younger patients seemed to be more resistant. Also, larger doses should be given to larger individuals. It seems that aspirin preparations and doses need to be tailored to the individual patient.
The majority of chronic stable coronary artery disease patients given 75 mg of EC aspirin daily have adequate inhibition of COX, but younger, heavier, and post MI patients may not.Subscribe Now for Access
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