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 .
Variability in the pharmacokinetics and pharmacodynamics of low dose aspirin in healthy male volunteers.
Data describing the pharmacokinetics and pharmacodynamics of low dose aspirin ( acetylsalicylic acid ; ASA ) are limited . This single-center study was design ed to determine the rate and extent of oral absorption of 80-mg ASA tablets in healthy , young male subjects and to assess the intra- and inter-subject variability of ASA pharmacokinetics and platelet aggregation effects . Ten subjects each received a single , open-label , oral 80-mg ASA dose on three separate days . Each dose was separated by a 2-week washout interval . Blood sample s for pharmacokinetic determinations of ASA and its metabolite , salicylic acid ( SA ) and platelet aggregation studies were obtained at scheduled timepoints before and up to 24 hours after each dose . Peak plasma ASA levels of 1 microgram/mL were achieved within 30 minutes . Peak plasma SA levels of approximately 4 micrograms/mL were attained in 1 hour . The terminal half-lives ( t1/2 ) of ASA and SA were 0.4 and 2.1 hours , respectively . Both ASA and SA pharmacokinetics and the platelet aggregation response to ASA exhibited considerable intra- and inter-subject variability . Inhibition of platelet aggregation was found to relate with ASA area under the plasma concentration versus time curve ( AUC )
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 .