Antiplatelet Therapy: Aspirin
- Volume 15 - Issue 4 - April, 2003
- Posted on: 8/1/08
- 0 Comments
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What is the Appropriate Aspirin Dose? At the start of the 20th century, Bayer aspirin was originally sold in the U.S as a 5 grain tablet (approximately 325 mg) because that particular size happened to make a convenient pill. This 325 mg dose is still primarily used today. A 1985 study presented some early data on the aspirin dose necessary to inhibit platelet thromboxane production.22,23 The data show that approximately 12 mg was the daily dose required for chronic therapy to completely inhibit thromboxane metabolism. As a single dose, approximately 100 mg were required. Obviously, there was a variability among patients, but in these small studies of volunteers, the data suggest a considerably lower dose than is currently utilized. The large Dutch TIA trial involving 3,131 patients who had a recent TIA or minor stroke, made head-to-head comparisons between 283 mg of aspirin and a very low 30 mg dose of aspirin.24 If anything, the trend showed a benefit with the 30 mg daily dose of aspirin, but there was essentially no difference over time. A substudy of 31 patients showed identical levels of suppression (99%) of thromboxane metabolite.
Several meta-analyses have been conducted analyzing the relationship between aspirin dose and efficacy.25 A meta-analysis of 10 randomized trials showed a consistent benefit of aspirin with no significant difference based on low, medium, or high doses (Figure 7). Although there was no clear efficacy dose-response — at least over 30 mg — there was a clear dose response in terms of side effects. In the UK-TIA trial,26 patients either received placebo, high-dose aspirin (600 mg b.i.d.), or low-dose aspirin (300 mg q.d.). Each increase in the dose of aspirin was associated with an increased occurrence of side effects, i.e., gastrointestinal symptoms, hemorrhage, upper gastrointestinal symptoms, and constipation (Figure 8).
Finally, if the patient is an aspirin non-responder, can the dose simply be increased? Two very small trials have suggested this to be the case. One of these trials involved 107 patients with prior stroke, all of whom received < 325 mg aspirin daily.27 At that dose, approximately 80% of the patients were completely inhibited. Those who were not inhibited received gradually escalated doses of aspirin, up to 1,300 mg/day — a dose at which only 3 patients were considered non-responders. Small studies like these suggest that there may be a dose response, but if that is true, the trend would typically be in favor of a higher dose of aspirin in order to cover for some aspirin non-responders — which has not been the case.
Risk of bleeding with aspirin during CABG. More than 20 studies have focused on the risk of bleeding with aspirin use. Most of the early studies suggest that there is an increased risk, while a majority of the later studies show no increased risk of bleeding with aspirin in the peri-operative period. A large, single-center study published in the Annals of Surgery in 2002 involved nearly 2,000 aspirin users at the time of surgery.28 It compared outcomes in over 700 patients who had received no peri-operative aspirin. The results showed a significant increase in the need for blood transfusions, other blood products besides red blood cells, and re-operation for bleeding in aspirin users compared with non-users (Figure 9). The absolute numbers were small, but with multivariate analysis, prior aspirin use was a significant predictor of the need for blood transfusions in the peri-operative period.