A patient-level analysis of more than 100,000 people published in The Lancet argues for a more individualized approach to aspirin dosing based on body size.
Low doses (75-100 mg per day) were found to be ineffective for people above 154 pounds, while higher doses of aspirin only reduced cardiovascular events among patients with greater body size.
“Our findings that the clinical effectiveness of low-dose aspirin is reduced in people of greater weight and height, and that this association is reversed with higher doses, suggest the existence of a therapeutic window related to body size within which a given daily dose is most effective,” wrote lead author Peter M. Rothwell, MD, PhD, an Oxford researcher and clinical neurologist, and colleagues.
“Specifically, loss of efficacy can occur if the aspirin dose is too low or too high for body size, and other harms appear to result from excess dosing. Reductions in cardiovascular events and all-cause death at optimal doses for weight were substantial, highlighting the potential of more tailored aspirin dosing.”
The researchers analyzed data from 117,279 participants from 10 trials of aspirin as a primary prevention therapy against cardiovascular disease (CVD). They looked at the modifying effects of bodyweight and height on the effects of aspirin at different doses.
Among their findings:
- Once-daily, low-dose (75-100 mg) aspirin was associated with a 25 percent reduction in cardiovascular events among individuals weighing 50-69 kilograms, or about 110-152 pounds. However, there was no significant reduction in CVD events for those weighing above that cutoff—and those heavier individuals had a 1.33-fold risk of dying of their first cardiovascular event when compared to lighter individuals on a low-dose regimen.
- 325 mg of aspirin reduced cardiovascular events by 17 percent among people weighing 154 pounds or more, while 500 mg aspirin was associated with a 45 percent reduction for those weighing at least 198 pounds. These higher doses didn’t provide any additional protection for smaller patients in whom lower doses were sufficient, but did increase the risk of bleeding and sudden cardiac death.
- Similar associations were found for colorectal cancer risk, in that lighter individuals benefitted from low doses but higher doses were required for patients with greater bodyweight.
“Loss of effect at larger body size, driven more by weight and height than by BMI (body mass index), suggests insufficient systemic bioavailability of aspirin rather than increased platelet activation secondary to obesity,” the authors wrote. “Acetylation of platelet COX-1 in the portal circulation alone might not fully account for the effect of aspirin on cardiovascular events, at least with daily dosing, and some systemic bioavailability might be required to inhibit COX-1 in megakariocytes, partially inhibit extra-platelet COX, or increase endothelial nitric oxide formation.”
Rothwell et al. said their results indicate a once-daily, low-dose aspirin regimen isn’t effective for preventing vascular events among 80 percent of men and almost 50 percent of women because they weigh above 154 pounds. In addition, aspirin’s protectiveness against stroke—thought to be more pronounced in women—was similar for both sexes when bodyweight was accounted for.
“Given that aspirin's effects on other outcomes, including cancer, also showed interactions with body size, a one-dose-fits-all approach to aspirin is unlikely to be optimal,” Rothwell and coauthors wrote.
Daniel joined TriMed’s Chicago editorial team in 2017 as a Cardiovascular Business writer. He previously worked as a writer for daily newspapers in North Dakota and Indiana.