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 .
Risk of aspirin-associated major upper-gastrointestinal bleeding with enteric-coated or buffered product
BACKGROUND Aspirin products are known to cause irritation and injury to the gastric mucosa . The belief that enteric-coated and buffered varieties are less likely to occasion major upper-gastrointestinal bleeding ( UGIB ) than plain aspirin was tested in data from a multicentre case-control study . METHODS 550 incident cases of UGIB admitted to hospital with melaena or haematemesis and confirmed by endoscopy , and 1202 controls identified from population census lists , were interviewed about use of aspirin and other non-steroidal anti-inflammatory drugs ( NSAIDs ) during the 7 days before the onset of bleeding ( cases ) or interview ( controls ) . Relative risks of UGIB for each type of aspirin used regularly ( at least every other day ) were calculated overall , and according to dose , by multiple logistic regression , with control for age , sex , marital status , date , education , cigarette smoking , alcohol use , and use of NSAIDs . FINDINGS The relative risks of UGIB for plain , enteric-coated , and buffered aspirin at average daily doses of 325 mg or less were 2.6 , 2.7 , and 3.1 , respectively . At doses greater than 325 mg , the relative risk was 5.8 for plain and 7.0 for buffered aspirin ; there were insufficient data to evaluate enteric-coated aspirin at this dose level . There were no important differences in risk attributable to the three aspirin forms according to bleeding site ( gastric vs duodenal ) , or when users of NSAIDs were excluded . INTERPRETATION Use of low doses of enteric-coated or buffered aspirin carries a three-fold increase in the risk of major UGIB . The assumption that these formulations are less harmful than plain aspirin may be mistaken
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 .