The one-dose-fits-all approach to the use of aspirin to prevent cardiovascular events may limit aspirin's effectiveness in certain populations, possibly because of underdosing in patients with greater body size or overdosing in those with smaller body size. Using patient data from controlled clinical trials, researchers examined the modifying effects of body weight, height, body mass index, and other measures of body size on the effectiveness of low and higher dosages of aspirin in the primary and secondary prevention of cardiovascular events. They also examined the findings in trials of aspirin in the secondary prevention of stroke to validate the results of the primary outcome, and studied the effects of aspirin on the risks of colorectal and other cancers.

They identified 10 eligible trials comparing aspirin with controls (in most cases, placebo; in some cases, two doses of aspirin were compared) in the primary prevention of cardiovascular events.

The ability of low-dose (75 to 100 mg) aspirin to reduce cardiovascular events decreased as body weight increased, the greatest benefit seen in participants weighing between 50 and 69 kg (110 and 179 lb). Low-dose aspirin was ineffective in 80% of men and nearly 50% of women weighing more than 70 kg (180 lb), particularly those who smoked or took enteric-coated aspirin, and even increased the rate of death from a first cardiovascular event. Higher doses, in contrast, were effective only in participants weighing more than 70 kg. Similar results were found in trials of secondary prevention of cardiovascular events and stroke and in studies of long-term risk of colorectal cancer, in which the effectiveness of low-dose aspirin was found to be lost in higher-weight individuals. Harms related to excess dosing were also noted, with an increase in sudden deaths at lower weight and an increase in short-term cancer risk at lower weight and shorter height in participants 70 years of age or older.

Given the substantial reductions in cardiovascular events and death with dosages optimized for weight, a tailored approach to aspirin dosing is likely to improve effectiveness, the authors conclude.-KR

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