Berent et al concluded that “there is no difference in antiplatelet response to aspirin 50 versus 100 mg or cardiovascular events (CV) over 5 years in patients with coronary heart disease.” However, there were 50% more patients with diabetes in the 100-mg group compared to the 50-mg group (24% vs 16%, respectively). It has been shown that patients with diabetes have a much higher prevalence of aspirin resistance. Therefore, more patients with diabetes in the 100-mg group biases the results in favor of a null effect between the doses, with respect to both outcomes.

In a trial of 25 patients with diabetes with coronary artery disease (CAD), aspirin 100 mg twice daily significantly reduced the high platelet reactivity seen with aspirin 100 mg/day (p = 0.025). Only 7 patients showed optimal platelet-inhibitor effects (collagen/epinephrine closure time ≥ 298 seconds at 8 am ), which increased to 10 patients taking 100 mg twice daily. The trial concluded that aspirin 100 mg twice daily significantly improves aspirin’s effect on platelets of patients with diabetes and CAD compared to once-daily dosing.

Aspirin resistance was tested in 123 patients (85.4% had coronary disease, and 30.1% were smokers) using aspirin reaction units. Seven of 8 nonresponders to 81 mg/day became responders to 325 mg/day. The investigators concluded that nonresponders to aspirin 81 mg/day frequently respond to 325 mg/day.

A prospective, open-label study in 20 patients with diabetes and CAD showed that aspirin administered once daily had no significant effect on decreasing platelet reactivity (collagen-induced aggregation and VerifyNow Aspirin [Accumetrics, Inc., San Diego, California]) with increasing doses. However, a significant reduction in platelet reactivity occurred if aspirin was given twice daily compared to once daily (81 mg/day vs 81 mg twice daily, p <0.05 for both assays, and 81 mg/day vs 162 mg twice daily, p <0.05 for both assays). Furthermore, serum thromboxane B ₂ levels decreased with increasing aspirin dose if given twice daily compared to once daily (p = 0.048 for the difference between 81 mg/day and 81 mg twice daily, p = 0.017 for the difference between 81 mg/day and 162 mg twice daily). The investigators concluded that low-dose aspirin twice daily resulted in greater platelet inhibition than once-daily administration in patients with diabetes and CAD.

Dalen concluded that for the primary prevention of myocardial infarction in men aged >50 years, a minimum dose of 160 mg of aspirin should be administered, and for women, >100 mg/day should be used. The results were from 5 randomized trials showing that aspirin 160 mg consistently lowered myocardial infarction in men and that doses of 75 to 100 mg were ineffective for the primary prevention of stroke in men and women. Dalen also concluded that the risk for bleeding is the same for 80 mg compared to 160 mg of aspirin. In summary, the most appropriate dose for the primary and secondary prevention of stroke and myocardial infarction is 160 mg/day according to Dalen.

In 468 consecutive patients with stable CAD, aspirin ≤100 mg/day was a univariate predictor of aspirin resistance (p = 0.004). Aspirin ≤100 mg/day was associated with a significantly higher prevalence of aspirin resistance compared to 150 mg/day and 300 mg/day (30.2% vs 16.7% vs 0%, p = 0.0062).

In summary, the previous data indicate that 160 mg/day of aspirin (either 160 mg/day or 81 mg twice daily) decreases aspirin resistance in patients with CAD compared to 81 mg day. Berent et al used doses of 50 mg in contrast to 100 mg/day, which did not show a difference. The null effects could have been a case of inappropriate comparison of aspirin doses (50 and 100 mg vs 81 and 160 mg) as well as inappropriate frequency of dosing (daily vs twice daily).