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Thromb Haemost 2022; 122(09): 1443-1453
DOI: 10.1055/s-0042-1743469
Invited Mini Series: Novel Clinical Concepts in Thrombosis

Aspirin for Primary Cardiovascular Prevention in Patients with Diabetes: Uncertainties and Opportunities

Mélina Del Bianco-Rondeau
1   Faculty of Pharmacy, Université de Montréal, Montreal, Québec, Canada
,
Maxime Robert-Halabi
2   Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada
3   Department of Medicine, Montreal Heart Institute, Montreal, Québec, Canada
,
Samara Bloom
2   Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada
4   Research Center, Montreal Heart Institute, Montreal, Québec, Canada
,
Remi Rabasa-Lhoret
5   Institut de Recherche Clinique de Montréal, Montreal, Québec, Canada
,
Jean-Claude Tardif
2   Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada
3   Department of Medicine, Montreal Heart Institute, Montreal, Québec, Canada
4   Research Center, Montreal Heart Institute, Montreal, Québec, Canada
,
Marie Lordkipanidzé 
1   Faculty of Pharmacy, Université de Montréal, Montreal, Québec, Canada
4   Research Center, Montreal Heart Institute, Montreal, Québec, Canada
,
Guillaume Marquis-Gravel 
2   Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada
3   Department of Medicine, Montreal Heart Institute, Montreal, Québec, Canada
4   Research Center, Montreal Heart Institute, Montreal, Québec, Canada
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Abstract

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.

Keywords

diabetes mellitus - aspirin resistance - aspirin - antiplatelet agent - platelet


Publication History

Received: 07 September 2021

Accepted: 14 January 2022

Article published online:
04 March 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
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