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 .
Risks of gastrointestinal bleeding during secondary prevention of vascular events with aspirin--analysis of gastrointestinal bleeding during the UK-TIA trial.
From 1979 to 1985 2435 patients having had transient ischaemic attacks ( TIAs ) or minor ischaemic strokes , were enrolled in the UK TIA trial and were r and omised to receive either aspirin 300 mg , daily or aspirin 1200 mg or placebo . Analysis of reported upper gastrointestinal bleeding events ( defined as haematemesis or melaena , or both ) showed a risk of bleeding in a dose dependent manner , odds ratios ( 95 % CI ) for 300 mg of aspirin = 3.3 ( 1.2 to 9.0 ) and for 1200 mg = 6.4 ( 2.5 to 16.5 ) and , as would be expected , an increased risk of hospitalisation because of bleeding also in a dose dependent manner , odds ratio = 3.6 ( 0.7 to 17.2 ) for 300 mg and 8.7 ( 2.0 to 37.6 ) for 1200 mg . Further analysis suggested greater risks of bleeding from duodenal ulcers than gastric ulcers and that bleeding is more likely early in the course of treatment with aspirin used as secondary prevention . There was also an increased risk of lower gastrointestinal bleeding , defined as fresh blood per rectum for both doses of aspirin , odds ratio 1.8 ( 0.5 to 6.1 ) for 300 mg of aspirin , and 1.5 ( 0.4 to 5.3 ) for 1200 mg of aspirin
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 .