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 .
Randomized, Double-Blind, Placebo-Controlled, International Trial of the Oral IIb/IIIa Antagonist Lotrafiban in Coronary and Cerebrovascular Disease
Background —This is the primary report of the large-scale evaluation of lotrafiban , an orally administered IIb/IIIa receptor antagonist , a unique trial with respect to the platelet antagonist , protocol design , and inclusion of cerebrovascular disease in a significant proportion of patients . Methods and Results — Patients with vascular disease were r and omized to lotrafiban 30 or 50 mg BID on the basis of age and predicted creatinine clearance or placebo in addition to aspirin at a dose ranging from 75 to 325 mg/d at the discretion of the physician-investigator . Follow-up was for up to 2 years . The primary end point was the composite of all-cause mortality , myocardial infa rct ion , stroke , recurrent ischemia requiring hospitalization , and urgent revascularization . Of 9190 patients enrolled from 23 countries and 690 hospitals , 41 % had cerebrovascular disease at the time of entry , and 59 % had coronary artery disease .  Death occurred in 2.3 % of placebo-assigned patients and 3.0 % of lotrafiban-group patients ( hazard ratio 1.33 , 95 % CI 1.03 to 1.72 , P = 0.026 ) , and the cause of excess death was vascular related . There was no significant difference in the primary end point ( 17.5 % compared with 16.4 % , respectively ; hazard ratio 0.94 , 95 % CI 0.85 to 1.03 , P = 0.19 ) . Serious bleeding was more frequent in the lotrafiban group ( 8.0 % compared with 2.8 % ; P < 0.001 ) . Serious bleeding was more common among patients who received higher doses of aspirin ( > 162 mg/d ) , with or without lotrafiban . Conclusions —Lotrafiban , an orally administered platelet glycoprotein IIb/IIIa blocker , induced a 33 % increase in death rate , which was vascular in origin and not affected by the type of atherosclerotic involvement at entry to the trial . Although the dose of aspirin was not r and omly assigned , the finding of increased bleeding with doses > 162 mg/d is noteworthy
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 .