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Impact of diabetes mellitus on the pharmacodynamic effects of prasugrel and ticagrelor after switching from clopidogrel in patients with coronary artery disease

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Abstract

Switching P2Y12 inhibitors is common in clinical practice. However, data on the pharmacodynamic (PD) effects of switching in clinical settings characterized by high platelet reactivity, such as diabetes mellitus (DM), are limited. This is a post-hoc analysis from a prospective, randomized, open-label study conducted in coronary artery disease patients comparing the PD effects of loading dose (LD) and maintenance dose regimens of prasugrel vs ticagrelor according to DM status. A total of 110 patients were enrolled: 42 (38%) with DM and 68 (62%) without DM. All patients were on maintenance dual antiplatelet therapy with aspirin and clopidogrel. PD assessments were performed using whole blood vasodilator-stimulated phosphoprotein (VASP), with results quantified by the platelet reactivity index (PRI), VerifyNow P2Y12 (VN-P2Y12) with results reported as P2Y12 reaction units (PRU), and light transmittance aggregometry (LTA) following 20 and 5 µM adenosine diphosphate stimuli with results reported as maximum platelet aggregation (MPA). PD assessments were performed at baseline (while on clopidogrel), 30 min after LD, 2 h after LD, and 1 week after LD. Overall, platelet reactivity was higher in DM than in non-DM patients while on clopidogrel therapy. After switching to either prasugrel or ticagrelor, platelet reactivity dropped but remained significantly higher among patients with DM at 30 min with all tests (VN-PRU p < 0.01, MPA 20 µM p < 0.01, VASP-PRI p = 0.02) and at 2 h with VN-PRU (p < 0.01) and LTA-MPA 20 µM (p < 0.01) but not with VASP-PRI (p = 0.19). There were no significant differences between prasugrel and ticagrelor both among patients with or without DM, except for lower LTA-MPA 20 at 30 min (p < 0.01) among non-DM patients treated with prasugrel. Patients with DM treated with clopidogrel have higher platelet reactivity compared to patients without DM. Although platelet reactivity markedly reduces to a similar extent after switching to prasugrel or ticagrelor, patients with DM persist with increased platelet reactivity compared to patients without DM.

Study registration: ClinicalTrials.gov identifier: NCT01852175

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Acknowledgements

The present study was funded by Institutional Grant of the University of Florida College of Medicine-Jacksonville.

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Authors and Affiliations

  1. Division of Cardiology, University of Florida College of Medicine-Jacksonville, 655 West 8th Street, Jacksonville, FL, 32209, USA

    Mattia Galli, Fabiana Rollini, Latonya Been, Martin M. Zenni, Dominick J. Angiolillo & Francesco Franchi

  2. Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy

    Mattia Galli

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  1. Mattia Galli
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  2. Fabiana Rollini
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  4. Martin M. Zenni
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Correspondence to Francesco Franchi.

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Conflict of interest

M.G. declares that he has received honoraria from Terumo. F.F. declares that he has received payment as an individual for consulting fee or honorarium from AstraZeneca, Bayer and Sanofi. Institutional payments for grants from PLx Pharma, and The Scott R. MacKenzie Foundation. F.R. declares that he has received honoraria from Chiesi. D.J.A. declares that he has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, and Sanofi,. D.J.A. also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, Renal Guard Solutions and Scott R. MacKenzie Foundation. The remaining authors report no disclosures.

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Galli, M., Rollini, F., Been, L. et al. Impact of diabetes mellitus on the pharmacodynamic effects of prasugrel and ticagrelor after switching from clopidogrel in patients with coronary artery disease. J Thromb Thrombolysis 54, 461–469 (2022). https://doi.org/10.1007/s11239-022-02696-4

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