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 .
Sex differences in platelet reactivity and response to low-dose aspirin therapy.
CONTEXT Recent r and omized trials suggest that women may not accrue the same cardioprotective benefits as men do from low-dose aspirin therapy used in primary prevention . Failure of aspirin to suppress platelet aggregation in women is one hypothesized mechanism . OBJECTIVE To examine differential platelet reactivity to low-dose aspirin therapy by sex . DESIGN , SETTING , AND PARTICIPANTS A clinical trial of aspirin at 81 mg/d for 14 days was conducted in 571 men and 711 women . Baseline and post-aspirin therapy measures included platelet aggregation to arachidonic acid , adenosine diphosphate , epinephrine , and platelet function analyzer closure time . MAIN OUTCOME MEASURE Sex differences in cyclooxygenase 1 ( COX-1 ) direct and indirect platelet activation pathways before and after administration of aspirin . RESULTS In 10 of the 12 platelet agonist exposures , women 's platelets were significantly more reactive at baseline . However , after aspirin therapy , the percent aggregation to arachidonic acid ( the direct COX-1 pathway ) decreased more in women than in men ( P<.001 ) and demonstrated near total suppression of residual platelet reactivity in both men and women . In COX-1 indirect pathways , women experienced the same or more platelet inhibition than men in 8 of the 9 assays yet retained modestly greater platelet reactivity after aspirin therapy . In multivariable analysis , female sex significantly predicted aggregation to 2 muM and 10 muM of adenosine diphosphate ( P = .02 and < .001 , respectively ) and collagen at 5 mug/mL ( P<.001 ) independent of risk factors , age , race , menopausal status , and hormone therapy . CONCLUSIONS Women experienced the same or greater decreases in platelet reactivity after aspirin therapy , retaining modestly more platelet reactivity compared with men . However , most women achieved total suppression of aggregation in the direct COX-1 pathway , the putative mechanism for aspirin 's cardioprotection
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 .