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 .
A randomized factorial trial of reperfusion strategies and aspirin dosing in acute myocardial infarction. The DUCCS-II Investigators.
The focus of new research efforts to improve the morbidity and mortality associated with acute myocardial infa rct ion ( AMI ) has turned to adjuvant agents that show promise of improving outcomes following coronary thrombolysis . We enrolled 162 patients with AMI in a r and omized trial comparing front-loaded tissue-plasminogen activator ( t-PA ) plus weight-adjusted heparin with anisoylated plasminogen streptokinase activator complex ( APSAC ) without heparin as well as st and ard-dose ( 325 mg ) and low-dose ( 81 mg ) aspirin . The primary end point was an in-hospital morbidity profile ; secondary end points were clinical and angiographic potency and hemorrhagic events . Selected sites performed an electrocardiographic sub study to determine the time to 50 % ST-segment recovery and the time to steady state . Although the trial was terminated when the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries-I trial showed that t-PA had a significant mortality advantage over streptokinase , important trends were evident . Patients given t-PA and heparin were better anticoagulated ( p = 0.001 ) , yet AP-SAC-treated patients had more bleeding complications . The primary end point favored t-PA ( 25.4 % vs 31.3 % ) , and the secondary end points were similar in both groups . In the electrocardiographic sub study , the t-PA group achieved both 50 % ST-segment recovery and steady-state recovery sooner than the APSAC group . Patients taking low-dose aspirin  had lower in-hospital mortality and less recurrent ischemia but more strokes than the st and ard-dose aspirin group . Thus , this trial demonstrated trends favoring front-loaded t-PA with weight-adjusted heparin over APSAC without heparin in the treatment of AMI . The use of low-dose aspirin did not appear to impose a loss of protection from adverse events , nor did st and ard-dose aspirin increase serious bleeding
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 .