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 Acquisition A systematic review of the English-language literature was undertaken using MEDLINE and EMBASE (searched through February 2007) and the search term aspirin or acetylsalicylic acid and dose. The search was limited to clinical trials and was extended by a review of bibliographies of pertinent reports of original data and review articles. Published prospective studies using different aspirin dosages in the setting of cardiovascular disease were included.
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. In the United States, 81 mg/d of aspirin is prescribed most commonly (60%), followed by 325 mg/d (35%). 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.