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Platelet reactivity in response to aspirin and ticagrelor in African-Americans and European-Americans

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Abstract

Platelet gene polymorphisms are associated with variable on-treatment platelet reactivity and vary by race. Whether differences in platelet reactivity and aspirin or ticagrelor exist between African-American and European-Americans remains poorly understood. Biological samples from three prior prospective antiplatelet challenge studies at the Duke Clinical Research Unit were used to compare platelet reactivity between African-American and European-American subjects. Platelet reactivity at baseline, on-aspirin, on-ticagrelor, and the treatment effect of aspirin or ticagrelor were compared between groups using an adjusted mixed effects model. Compared with European-Americans (n = 282; 50% female; mean ± standard deviation age, 50 ± 16), African-Americans (n = 209; 67% female; age 48 ± 12) had lower baseline platelet reactivity with platelet function analyzer-100 (PFA-100) (p < 0.01) and with light transmission aggregometry (LTA) in response to arachidonic acid (AA), adenosine diphosphate (ADP), and epinephrine agonists (p < 0.05). African-Americans had lower platelet reactivity on aspirin in response to ADP, epinephrine, and collagen (p < 0.05) and on ticagrelor in response to AA, ADP, and collagen (p < 0.05). The treatment effect of aspirin was greater in European-Americans with an AA agonist (p = 0.002). Between-race differences with in vitro aspirin mirrored those seen in vivo. The treatment effect of ticagrelor was greater in European-Americans in response to ADP (p < 0.05) but with collagen, the treatment effect was greater for African-Americans (p < 0.05). Platelet reactivity was overall lower in African-Americans off-treatment, on aspirin, and on ticagrelor. European-Americans experienced greater platelet suppression on aspirin and on ticagrelor. The aspirin response difference in vivo and in vitro suggests a mechanism intrinsic to the platelet. Whether the absolute level of platelet reactivity or the degree of platelet suppression after treatment is more important for clinical outcomes is uncertain.

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Abbreviations

AA:

Arachidonic acid

AUC:

Area under the curve

AU*min:

Percent aggregation units per minute

ADP:

Adenosine diphosphate

CAD:

Coronary artery disease

COL:

Collagen

COX-1:

Cyclooxygenase-1

DM:

Diabetes mellitus

EPI:

Epinephrine

HTPR:

High on-treatment platelet reactivity

LTA:

Light transmission aggregometry

LTPR:

Low on-treatment platelet reactivity

PFA:

Platelet function analyzer

PLATO:

Platelet Inhibition and Patient Outcomes trial

PRP:

Platelet rich plasma

vWF:

Von Willebrand factor

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Acknowledgements

No other persons besides the authors have made substantial contributions to this manuscript.

Funding

This research was supported by the National Institutes of Health R01HL118049 and National Center for Research Resources, a component of the NIH 5UL1RR024128 Grant (Dr. Voora); the National Institutes of General Medical Sciences 5RC1GM091083 Grant (Dr. Ginsburg); the Centers for Disease Control and Prevention Grant 5U01DD000014 (Dr. Ortel), and the 2012/0003R Grant from Duke-National University Singapore (Dr. Ru San)

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Authors and Affiliations

  1. Center for Applied Genomics & Precision Medicine, Duke University, 2187 CIEMAS, Campus Box 3382, Durham, NC, 27708, USA

    Holly J. Knickerbocker, Geoffrey S. Ginsburg & Deepak Voora

  2. Division of Cardiology, Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA

    Margaret Infeld

  3. Division of Cardiology, Department of Medicine, Duke University, Durham, NC, USA

    Kevin A. Friede, Geoffrey S. Ginsburg & Deepak Voora

  4. Department of Cardiology, National Heart Centre, Singapore, Singapore

    Tan Ru San

  5. Division of Hematology, Duke University, Durham, NC, USA

    Thomas L. Ortel

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  1. Margaret Infeld
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Infeld, M., Friede, K.A., San, T.R. et al. Platelet reactivity in response to aspirin and ticagrelor in African-Americans and European-Americans. J Thromb Thrombolysis 51, 249–259 (2021). https://doi.org/10.1007/s11239-020-02327-w

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