The available evidence , predominantly from secondary -prevention observational studies , supports that dosages greater than 75 to 81 mg/d do not enhance efficacy , whereas larger dosages are associated with an increased incidence of bleeding events , primarily related to gastrointestinal tract toxicity .
CONCLUSIONS Currently available clinical data do not support the routine , long-term use of aspirin dosages greater than 75 to 81 mg/d in the setting of cardiovascular disease prevention .
Higher dosages , which may be commonly prescribed , do not better prevent events but are associated with increased risks of gastrointestinal bleeding
CONTEXT More than 50 million US adults take aspirin regularly for long-term prevention of cardiovascular disease , typically either 81 mg/d or 325 mg/d .
Controversy remains regarding the most appropriate long-term daily dose .
OBJECTIVE To review the mechanism of action of aspirin and the clinical literature for relationships among  aspirin dosage , efficacy , and safety .
EVIDENCE SYNTHESIS Although pharmacodynamic data demonstrate that long-term aspirin dosages as low as 30 mg/d are adequate to fully inhibit platelet thromboxane production , dosages as high as 1300 mg/d are approved for use .
Anti-Platelet Effects of 100 mg Alternate Day Oral Aspirin: A Randomized, Double-Blind, Placebo-Controlled Trial of Regular and Enteric Coated Formulations in Men and Women
Aim While regular use of low-dose aspirin has been recommended for several groups of patients at risk of vascular occlusion , the optimal dose of aspirin to produce a cardiovascular benefit whilst minimizing side effects is uncertain . Further , while enteric coated preparations may reduce gastrointestinal symptoms , the antiplatelet effects of these formulations have not been completely tested . In addition , exceptionally few data relating to these issues have been available in women . Methods To determine whether a 100 mg alternate day dose of aspirin given in regular and enteric coated formulations for a 2-week period is sufficient to inhibit platelet function in men and women , a r and omized , double-blind , placebo-controlled trial was conducted among 22 healthy volunteers evaluating the effects of these preparations on platelet aggregation induced by arachidonic acid , adenosine diphosphate , and epinephrine , and on plasma concentrations of thromboxane and prostacyclin . Results During the active aspirin phase of the study , all subjects demonstrated a clinical anti-platelet effect as evidence d by failure of the platelets to aggregate in the presence of at least one platelet agonist , and mean thromboxane and prostacyclin levels decreased to 7.5 and 15.6 % of baseline , respectively ( both P < 0.001 ) . After cessation of active aspirin , all subjects had full recovery of platelet function as well as thromboxane and prostacyclin production . There were virtually no differences between regular and enteric coated formulations , or between men and women . Conclusion These data indicate that an alternate day regimen of 100 mg aspirin given in either regular or enteric coated formulation is adequate to achieve functional platelet inhibition . The clinical efficacy of this dose and formulation of aspirin is being tested in the ongoing Women 's Health Study , a r and omized , double-blind , placebo-controlled trial of 40 000 female health professionals design ed in part to assess the benefits and risks of 100 mg alternate day aspirin in the primary prevention of cardiovascular disease
The available evidence , predominantly from secondary -prevention observational studies , supports that dosages greater than 75 to 81 mg/d do not enhance efficacy , whereas larger dosages are associated with an increased incidence of bleeding events , primarily related to gastrointestinal tract toxicity .
CONCLUSIONS Currently available clinical data do not support the routine , long-term use of aspirin dosages greater than 75 to 81 mg/d in the setting of cardiovascular disease prevention .
Higher dosages , which may be commonly prescribed , do not better prevent events but are associated with increased risks of gastrointestinal bleeding
CONTEXT More than 50 million US adults take aspirin regularly for long-term prevention of cardiovascular disease , typically either 81 mg/d or 325 mg/d .
Controversy remains regarding the most appropriate long-term daily dose .
OBJECTIVE To review the mechanism of action of aspirin and the clinical literature for relationships among  aspirin dosage , efficacy , and safety .
EVIDENCE SYNTHESIS Although pharmacodynamic data demonstrate that long-term aspirin dosages as low as 30 mg/d are adequate to fully inhibit platelet thromboxane production , dosages as high as 1300 mg/d are approved for use .