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 .
Effects of low-dose aspirin on in vitro platelet aggregation in the early minutes after ingestion in normal subjects.
Aspirin interferes with platelet aggregation by inhibiting the metabolism of arachidonic acid to thromboxane A2 . Although both high- and low-dose aspirin therapies are effective for secondary prophylaxis in patients with atherosclerotic vascular disease , the acute response to low-dose aspirin therapy is controversial . Eighteen volunteer subjects ingested 81 , 162 , or 324 mg of aspirin in a longitudinal crossover study design . Initial doses were r and omly assigned and dosing intervals were separated by 2 weeks . Platelet aggregation in response to 0.9 mM arachidonic acid was measured at baseline , 15 , 30 , 60 , and 90 minutes after ingestion . Thromboxane B2 production was assayed on simultaneously obtained sample s after stimulation with arachidonic acid . The median inhibition of aggregation was 97 % , 97 % , and 97 % 15 minutes after ingestion of 81 , 162 , and 324 mg , respectively . Four subjects had < 20 % inhibition 15 minutes after ingesting 81 mg , but all 4 had > 90 % inhibition after 30 minutes . Thromboxane B2 production declined by > 93 % in all subjects at each dose . There was no difference between doses in inhibition of thromboxane B2 production
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 .