The researchers suggest from these findings that a one-dose-fits-all approach to aspirin is unlikely to be optimal, and a more tailored strategy is required.
According to a commentary, weight can affect drug distribution and clearance, and is known to modulate platelet inhibition by clopidogrel and prasugrel. With regard to aspirin, it adds that extensive clearance by esterases in the intestine, plasma, blood cells, and the liver results in a systemic bioavailability of just 50%, therefore it postulates that individuals with a larger body mass would have a greater quantity of these esterases than would smaller individuals, resulting in reduced aspirin bioavailability. It notes that aspirin irreversibly acetylates COX-1 in platelets that are unable to synthesise new enzyme, thus, low doses of aspirin can inhibit platelet function as long as more platelets are inhibited than are newly released from megakaryocytes. This inhibition can occur presystemically before inactivation by liver esterases. Prostacyclin, the vascular COX product intended to be spared by use of low doses of aspirin, is a potent platelet inhibitor and a central molecule in the important negative feedback mechanism that limits the growth of thrombi at sites of vascular injury. It therefore suggests that the apparent lack of efficacy of intermediate-dose and high-dose aspirin in individuals weighing less than 70 kg raises the question of whether these treatment failures might reflect inhibition of vascular prostacyclin because of the increased systemic bioavailability of aspirin in this subgroup. It questions how weight-adjusted dosing of aspirin might affect bleeding risk, particularly as 80% of men and nearly 50% of women in the analysis weighed ≥70 kg, and adjusted dosing would result in increased daily doses of aspirin in the majority of patients, which would be expected to affect bleeding risk. It concurs with the researchers that bodyweight should be considered in ongoing and future randomised clinical trials that address aspirin dosing in cardiovascular prevention to clarify how weight-adjusted dosing will affect both benefit and risk. It concludes that this study provides provocative findings, with the potential to substantially affect public health, but further research is needed to establish whether weight-adjusted dosing of aspirin should be incorporated into clinical care.