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 .
Aspirin therapy: optimized platelet inhibition with different loading and maintenance doses.
Inhibition of cyclooxygenase by aspirin has been shown to be beneficial in clinical situations such as acute myocardial infa rct ion or unstable angina . The precise effect of various doses of aspirin on acute and long-term inhibition of platelet aggregation and thromboxane synthesis remains unclear . In this study we evaluated the effect of oral aspirin ( 0 , 40 , 100 , 300 , or 500 mg ) as the initial loading dose in combination with different maintenance doses of aspirin ( 0 , 40 , or 100 mg/day ) for 14 days on platelet function in healthy men .  Bleeding time 2 or 24 hours after the first aspirin administration was significantly increased for 300 and 500 mg aspirin ( p < 0.01 ) . Two hours after the first administration of 100 , 300 , and 500 mg aspirin , a significant inhibition of collagen-induced platelet aggregation ( ED50 collagen : from 3 + /- 1 to 17 + /- 2 , 24 + /- 3 , 22 + /- 3 micrograms/ml , respectively ) was seen . At the same time serum thromboxane B2 synthesis was inhibited by more than 99 % with 300 and 500 mg aspirin . At the end of the 14-day observation period , bleeding time was significantly prolonged for the different combinations of aspirin doses compared with initial values ( p < 0.01 ) . Collagen-induced platelet aggregation and serum thromboxane B2 synthesis were significantly inhibited for all aspirin combinations tested at 14 days ( p < 0.05 ) . The 40/40 mg aspirin combination was less effective , because it reached its maximal effect very late at day 7 of the observation period compared with the other combinations . ( ABSTRACT TRUNCATED AT 250 WORDS
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 .