Antiplatelet efficacy of ticagrelor versus clopidogrel in Mediterranean patients with diabetes mellitus and chronic coronary syndromes: A crossover pharmacodynamic investigation

Ana Lucrecia Marcano; Montserrat Gracida; Gerard Roura; Josep Gomez-Lara; Rafael Romaguera; Luis Teruel; Lara Fuentes; Guillem Muntané-Carol; Oona Meroño; Silvia Gabriela Sosa; Joan Antoni Gómez-Hospital; Josep Comin-Colet; José Luis Ferreiro

doi:10.3389/fcvm.2022.1057331

Antiplatelet efficacy of ticagrelor versus clopidogrel in Mediterranean patients with diabetes mellitus and chronic coronary syndromes: A crossover pharmacodynamic investigation

Front Cardiovasc Med. 2022 Nov 22:9:1057331. doi: 10.3389/fcvm.2022.1057331. eCollection 2022.

Authors

Ana Lucrecia Marcano^{1

2}, Montserrat Gracida^{1

2}, Gerard Roura^{1

2}, Josep Gomez-Lara^{1

2}, Rafael Romaguera^{1

2}, Luis Teruel^{1

2}, Lara Fuentes^{1

2}, Guillem Muntané-Carol^{1

2}, Oona Meroño^{1

2

3}, Silvia Gabriela Sosa^{1

2}, Joan Antoni Gómez-Hospital^{1

2}, Josep Comin-Colet^{2

4}, José Luis Ferreiro^{2

4}

Affiliations

¹ Department of Cardiology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain.
² Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
³ Faculty of Medicine, University of Vic-Central University of Catalonia, Barcelona, Spain.
⁴ Department of Cardiology, Bellvitge University Hospital, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, L'Hospitalet de Llobregat, Barcelona, Spain.

Abstract

Introduction: Patients with diabetes mellitus (DM) have augmented platelet reactivity and diminished responsiveness to clopidogrel. Ticagrelor, a more potent P2Y₁₂ inhibitor, is clinically superior to clopidogrel in acute coronary syndromes, although its role in chronic coronary syndromes (CCS) is still the subject of debate. The aim of this investigation was to compare the pharmacodynamic effectiveness of ticagrelor and clopidogrel in Mediterranean DM patients with CCS.

Materials and methods: In this prospective, randomized, crossover study, patients (n = 20) were randomized (1:1) to receive, on top of aspirin therapy, either ticagrelor 180 mg loading dose (LD)/90 mg maintenance dose (MD) b.i.d. or clopidogrel 600 mg LD/75 mg MD o.d. for 1 week in a crossover fashion with a 2-4 week washout period between regimens. Platelet function measurements were performed at 4 timepoints in each period (baseline, 2 h and 24 h after LD, and 1 week), including light transmission aggregometry (LTA, primary endpoint), VASP assay, Multiplate and VerifyNow P2Y₁₂.

Results: The ticagrelor LD achieved greater platelet inhibitory effect than clopidogrel LD, assessed with LTA (20 μM ADP as agonist), at 2 h (34.9 ± 3.9% vs. 63.6 ± 3.9%; p < 0.001) and 24 h (39.4 ± 3.5% vs. 52.3 ± 3.8%; p = 0.014). After 1 week of therapy, platelet reactivity was again significantly inferior with ticagrelor compared to clopidogrel (30.7 ± 3.0% vs. 54.3 ± 3.0%; p < 0.001). The results were consistent with the other platelet function assays employed.

Conclusion: In Mediterranean patients with DM and CCS, ticagrelor provides a more potent antiplatelet effect than clopidogrel after the LD and during the maintenance phase of therapy.

Clinical trial registration: [ClinicalTrials.gov], identifier [NCT02457130].

Keywords: antiplatelet therapy; chronic coronary syndrome; diabetes mellitus; high platelet reactivity; ticagrelor.

Associated data

ClinicalTrials.gov/NCT02457130