Are We Underdosing Aspirin?

August 22, 2018

Written by Thomas Davis

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A low daily dose of aspirin (75-100mg) prevents cardiovascular events only in patients weighing < 70 kg. Higher doses are required in patients weighing more.

Why does this matter?
The optimal dose of aspirin may not be as simple as “a daily aspirin.” Obesity and increased BMI are associated with reduced inhibition of COX-1. Increased lean body mass may decrease bioavailability. Studies establishing the efficacy of aspirin in primary prevention of cardiovascular events used a uniform dose within each trial. However, the dose varied among trials. Does pooling these trials together shed any insight into the optimal aspirin dose?  

The Goldilocks principle for aspirin dosing
This study retrospectively analyzed individual patient data from ten prior studies (n = 117 279) that evaluated the efficacy of aspirin vs control in the primary prevention of cardiovascular events. The study stratified patients by weight, height, and other measures of body size (e.g. BMI) to determine their effects on high and low doses of aspirin. Among these variables, body weight had the strongest effect on modification of aspirin.

Pooled odds ratios (ORs) for the effect of low-dose aspirin on the risk of cardiovascular events were 0.77 (95% CI 0.68 – 0.87, p < 0.0001) among patients weighing less than 70 kg compared to 0.94 (95% CI 0.86 – 1.04, p = 0.24) among patients weighing greater than 70 kg. Higher doses of aspirin were needed to overcome increased weight. Aspirin 325mg appeared to be most efficacious among patients weighing over 70 kg (HR 0.83, p = 0.028), whereas 500mg had the greatest efficacy among patients weighing over 90 kg (HR 0.52, p = 0.017). Interestingly, there seemed to be no discernible benefit to high-dose aspirin compared to control among patients weighing under 70 kg. This suggests that aspirin has a therapeutic window: not too little, not too much.

Source
Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose: analysis of individual patient data from randomised trials.  Lancet. 2018 Aug 4;392(10145):387-399. doi: 10.1016/S0140-6736(18)31133-4. Epub 2018 Jul 17.
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Another Spoonful
The ACC summarized this on their journal scan as well.

Reviewed by Clay Smith