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 .
Aspirin absorption rates and platelet inhibition times with 325-mg buffered aspirin tablets (chewed or swallowed intact) and with buffered aspirin solution.
Large clinical trials such as the second International Study of Infa rct Survival routinely gave patients with myocardial infa rct ion a chewed aspirin , yet there are no data to show whether chewing of aspirin is better , or worse , than swallowing a whole tablet . We performed a r and omized , placebo-controlled study to determine whether chewing aspirin or administering it in solution accelerates its absorption and antiplatelet activity . On separate days , 12 fasting volunteers ingested 325 mg of buffered aspirin , either by chewing a tablet for 30 seconds before swallowing it with 4 ounces of water , swallowing a whole tablet with 4 ounces of water , or drinking 4 ounces of Alka Seltzer . Frequent blood sample s were obtained for serum aspirin , salicylate , and thromboxane B2 ( TxB2 ) concentrations . With all formulations of aspirin , serum TxB2 decreased 50 % when the plasma aspirin concentration reached approximately 1,000 ng/ml . A 50 % and 90 % decrease in serum TxB2 occurred more quickly after chewing a tablet than after a tablet was swallowed whole . For example , the t 50 % for serum TxB2 inhibition was 5.0 + /- 0.6 minutes with the chewed tablet versus 12.0 + /- 2.3 minutes when the tablet was swallowed ( p = 0.01 ) . A 50 % decrease in serum TxB2 occurred 7.6 + /- 1.2 minutes after Alka Seltzer solution ( p = 0.04 vs chewing a tablet ; p = 0.13 vs swallowing a whole tablet ) . Chewing an aspirin tablet is the most effective way of accelerating absorption of aspirin  into the blood and shortening the time required for an antiplatelet effect
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 .