Aspirin doses between 75 and 100 mg were only effective in preventing vascular events in patients weighing less than 70 kg, while higher doses of aspirin were only effective in patients weighing 70 kg or more, a study found.
Researchers analyzed randomized trials of aspirin as primary prevention for cardiovascular events, assessing the effects of aspirin doses of 100 mg or less, between 300 to 325 mg, and 500 mg or more by body weight broken down into 10-kg categories and height by 10-cm categories. Results were published July 12 by The Lancet. In 10 eligible trials of aspirin in primary prevention that included 117,279 participants, body weight varied fourfold and trial median weight ranged from 60.0 kg to 81.2 kg (P<0.0001).
The ability of 75 to 100 mg of aspirin to reduce cardiovascular events decreased with increasing weight, with benefit seen in people weighing 50 to 69 kg (hazard ratio [HR], 0.75; 95% CI, 0.65 to 0.85) but not in those weighing 70 kg or more (HR, 0.95; 95% CI, 0.86 to 1.04). The same was true for the outcome of vascular death (HR, 1.09; 95% CI, 0.93 to 1.29). Case fatality of a first cardiovascular event was increased with low-dose aspirin in people weighing 70 kg or more (odds ratio, 1.33; 95% CI, 1.08 to 1.64; P=0.0082).
Higher doses of aspirin (325 mg or more) had the opposite interaction with body weight, reducing cardiovascular events only in people who weighed more. Findings were similar in men and women, in people with diabetes, in trials of aspirin in secondary prevention, and in relation to height. Aspirin-mediated reductions in long-term risk of colorectal cancer were also weight dependent.
Stratification by body size also indicated harms due to excess dosing. Aspirin increased risk of sudden death in people at low weight for their dose (P=0.0018). Risk of all-cause death was increased in people weighing less than 50 kg who were receiving aspirin doses of 75 to 100 mg (HR,1.52; 95% CI, 1.04 to 2.21; P=0.031). In participants ages 70 years or older, the three-year risk of cancer was also increased with aspirin use (HR, 1.20; 95% CI, 1.03 to 1.47; P=0.02), particularly in those weighing less than 70 kg (HR, 1.31; 95% CI, 1.07 to 1.61; P=0.009) and in women (HR, 1.44; 95% CI, 1.11 to 1.87; P=0.0069).
The researchers wrote that “a one-dose-fits-all approach to aspirin is unlikely to be optimal, and a more tailored strategy is required.”
An editorial noted, “[W]eight-adjusted dosing would result in increased daily doses of aspirin in the majority of patients, which would be expected to affect bleeding risk. However, this association might not be linear because the authors observed that the bleeding risk on low-dose aspirin was elevated in patients weighing 70-90 kg despite the failure to prevent cardiovascular events.”