Key result
Once-daily low-dose enteric-coated aspirin may inadequately inhibit platelets in diabetes due to increased platelet turnover.
Why the study?
Recent trials failed to show a sizeable net clinical benefit for once-daily low-dose aspirin in primary prevention among patients with diabetes, prompting review of whether uniform dosing and formulations leverage its full potential.
Does aspirin reduce cardiovascular events in patients with diabetes without established atherosclerotic cardiovascular disease?
Does aspirin reduce cardiovascular events in patients with diabetes without established atherosclerotic cardiovascular disease?
While once-daily low-dose aspirin lacks a net clinical benefit for primary prevention in diabetes, altered platelet pharmacodynamics in this population suggest that twice-daily or non-enteric-coated formulations warrant further investigation.
May not support standard aspirin regimens for diabetes primary prevention; leaves open twice-daily dosing trials.
The use of the antiplatelet agent aspirin (acetylsalicylic acid) was previously routinely recommended for the primary prevention of cardiovascular (CV) events in patients with diabetes, but recent large-scale randomized trials have failed to demonstrate a sizeable net clinical benefit with a once-daily, low-dose (81-100 mg) regimen in this population. Previous pharmacokinetic and pharmacodynamic studies have suggested that the aspirin formulation (enteric-coated) and dosing schedule (once daily) studied in randomized trials for primary prevention of CV events defining contemporary clinical practice may not leverage the full potential of the drug, particularly in patients with diabetes. Indeed, the diabetic platelets bear characteristics that increase their thrombotic potential and alter their pharmacologic response to the drug. Consequently, the appropriateness of studying a uniform aspirin regimen in landmark primary prevention trials needs to be revisited. In this review, we present the evidence showing that diabetes not only increases baseline platelet reactivity, but also alters platelet response to aspirin through different mechanisms including a faster platelet turnover rate. Obesity, which is frequently associated with diabetes, also impacts its pharmacokinetics via an increase in distribution volume. Small-scale pharmacokinetic and pharmacodynamic studies have suggested that the relative aspirin resistance phenotype observed in patients with diabetes may be reversed with a twice-daily dosing schedule, and with nonenteric-coated aspirin formulations. Properly powered randomized controlled trials investigating the efficacy and safety of aspirin dosing schedules and formulations tailored to the population of patients with diabetes are urgently required to optimize patient care.
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Bianco-Rondeau et al. (2022) conducted a review in Diabetes mellitus. Aspirin vs. Placebo or no aspirin was evaluated. Once-daily low-dose enteric-coated aspirin may not provide optimal platelet inhibition in patients with diabetes due to increased platelet turnover and altered pharmacokinetics.
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