Dr. Campbell stated that:  "Recommendations vary but most state aspirin should be taken chronically at a dose anywhere between 75 mg and 325 mg daily, and some even include doses up to 1300 mg. We need to rethink this advice. We know that the risk of bleeding increases with higher doses, and this is now even more of an issue as more patients are also taking clopidogrel. But the beneficial effect of aspirin on clinical events does not appear to increase with increasing doses. So the guidelines should change to just recommend low doses — 75 or 81 mg. A lot of people buy aspirin over the counter and they need clear information about which dose to take." He added that there was much evidence that aspirin is beneficial for high-risk patients, but the evidence is less robust for lower risk patients (ie, primary prevention)."

Co-author Steven R. Steinhubl, MD, from the University of Kentucky in Lexington pointed out that even 75 or 81 mg is probably overdosing aspirin, as studies have shown that platelet thromboxane is completely inhibited with just 30 mg of aspirin taken long term. "The 75- to 81-mg dose has been arrived at completely arbitrarily as these doses are just one quarter of a 300- or 325-mg tablet," he said.

Dr. Campbell explained that the current results are consistent with those published by the Oxford Antithrombotic Trialists' Collaboration in 2002, but the analyses differed. "They compared trials using higher doses of aspirin with other trials using low doses of aspirin, but we looked at trials which included some patients taking high doses and others taking low doses. We also included a large amount of observational studies. So our findings agree with their findings but we've added a 'real world' spin," he said.

Dr. Campbell said, "There is a disconnect in the aspirin resistance story in that many small studies have shown a significant interpatient variability in platelet response to low-dose aspirin, but there is no clinical evidence that a higher dose would overcome this. There is no large trial that has suggested higher doses are any better in terms of clinical effects."

Practice Pearls

• Current clinical data support a daily dose of aspirin of 75 or 81 mg for CVD protection.
• Dosages of aspirin greater than 81 mg daily used for CVD protection are associated with significantly higher risk for bleeding vs lower doses.

JAMA. 2007;297:2018-2024.

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