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 .
Effects of Aspirin Dose When Used Alone or in Combination With Clopidogrel in Patients With Acute Coronary Syndromes: Observations From the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Study
Background —We studied the benefits and risks of adding clopidogrel to different doses of aspirin in the treatment of patients with acute coronary syndrome ( ACS ) . Methods and Results —In the Clopidogrel in Unstable angina to prevent Recurrent Events ( CURE ) trial , 12 562 patients with ACS using aspirin , 75 to 325 mg daily , were r and omized to clopidogrel or placebo for up to 1 year . In this analysis , patients were divided into the following 3 aspirin dose groups : ≤100 mg , 101 through 199 mg , and ≥200 mg . The combined incidence of cardiovascular death , myocardial infa rct ion , or stroke was reduced by clopidogrel regardless of aspirin dose , as follows : ≤100 mg , 10.5 % versus 8.6 % ( relative risk [ RR ] , 0.81 [ 95 % CI , 0.68 to 0.97 ] ) ; 101 to 199 mg , 9.8 % versus 9.5 % ( RR , 0.97 [ 95 % CI 0.77 to 1.22 ] ) ; and ≥200 mg , 13.6 % versus 9.8 % ( RR , 0.71 [ 95 % CI , 0.59 to 0.85 ] ) . The incidence of major bleeding increased with increasing aspirin dose both in the placebo group ( 1.9 % , 2.8 % , and 3.7 % , respectively ; P = 0.0001 ) and the clopidogrel group ( 3.0 % , 3.4 % , and 4.9 % , respectively ; P = 0.0009 ) ; thus , the excess risk with clopidogrel was 1.1 % , 1.2 % , and 1.2 % , respectively . The adjusted hazard ratio for major bleeding for the highest versus the lowest dose of aspirin was 1.9 ( 95 % CI 1.29 to 2.72 ) in the placebo group , 1.6 ( 95 % CI 1.19 to 2.23 ) in the clopidogrel group , and 1.7 ( 95 % CI 1.36 to 2.20 ) in the combined group . Conclusions —In patients with ACS , adding clopidogrel to aspirin is beneficial regardless of aspirin dose . Bleeding risks increase with increasing aspirin dose , with or without clopidogrel , without any increase in efficacy . Our findings suggest that the optimal daily dose of aspirin may be between 75 and 100 mg , with or without clopidogrel
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 .