Does platelet reactivity depend on chronic oral anticoagulation choice in patients undergoing pulmonary vein isolation?

    Authors

    Keywords

    direct oral anticoagulants, vitamin K antagonists, atrial fibrillation, pulmonary vein isolation, platelet reactivity

    DOI

    https://doi.org/10.15836/ccar2023.311

    Full Text

    **Introduction**: Direct oral anticoagulants (DOACs) are recommended in preference to vitamin K antagonists (VKA) in patients with atrial fibrillation (Afib) (1). There is no direct comparison between DOACs and substantial share of patients are still treated with VKAs due to certain comorbidities or financial reasons. Pulmonary vein isolation (PVI) is an established procedure to treat paroxysmal and persistent Afib but it increases thromboembolic risk (2). The aim of this study was to compare periinterventional platelet reactivity (PR) in Afib patients undergoing PVI on different chronic oral anticoagulation. **Patients and Methods**: PR was analyzed with Multiplate function analyzer in 136 patients undergoing PVI procedures in our institution. Blood samples were drawn before the procedure and on the following morning. ASPItest, ADPtest and TRAPtest were used as assays for the quantitative in vitro determination of PR triggered by arachidonic acid, adenosine diphosphate and thrombin receptor activating peptide-6, respectively. Fourty three patients (31.6%) were taking VKA, while 38 (27.9%), 29 (21.3%) and 26 (19.1%) patients were treated with dabigatran, rivaroxaban and apixaban, respectively. Edoxaban was not available during the investigation. **Results**: There was no significant difference in demographics between the groups. Patients on VKA had lower mean platelet volume (MPV) compared to patients on DOACs (9.9 vs 10.7-10.8 fL; p=0.020). Patients on xabans (rivaroxaban and apixaban) had lower baseline PR compared to VKA and dabigatran (**Table 1**). One day after PVI, there was no significant change from PR baseline in all four groups (**Figure 1**). ### TABLE 1: Study patient characteristics. | **Patients’ characteristics** | **VKA** **(n=43)** | **Dabigatran** **(n=38)** | **Rivaroxaban** **(n=29)** | **Apixaban (n=26)** | **p** | | --- | --- | --- | --- | --- | --- | | Age, years, mean (min-max) | 58.2 (36-73) | 61.7 (45-76) | 59.3 (42-77) | 60.1 (45-76) | 0.659 | | Men, n (%) | 31 (72.1) | 27 (71.1) | 22 (75.9) | 15 (57.7) | 0.487 | | BMI, kg/m2, mean (min-max) Paroxysmal Afib, n (%) | 29.2 (22.0-37.6) 32 (74.4) | 28.96 (21.4-38.1) 31 (81.6) | 27.68 (22.1-34.7) 20 (68.9) | 28.67 (23.1-38.3) 23 (88.5) | 0.560 0.307 | | Arterial hypertension, n (%) Hyperlipidemia, n (%) | 33 (76.7) 22 (51.2) | 30 (78.9) 23 (60.5) | 20 (68.9) 14 (48.3) | 24 (92.3) 12 (46.2) | 0.206 0.654 | | Diabetes mellitus, n (%) CrCl2DS2-VASc, mean (min-max) HAS-BLED, mean (min-max) | 1 (2.3) 2 (4.6) 1.72 (0-5) 0.77 (0-4) | 3 (7.9) 6 (15.8) 1.94 (0-6) 1.12 (0-3) | 4 (13.8) 4 (13.8) 2.07 (0-4) 1.00 (0-3) | 3 (11.5) 3 (11.5) 2.54 (0-5) 1.15 (0-4) | 0.310 0.343 0.095 0.238 | | Platelets, x109/L, mean (min-max) MPV, fL, mean (min-max) PR before PVI ASPItest, mean (U) ADPtest, mean (U) TRAPtest, mean (U) Periinterventional UFH administration, mean (IU) (min-max) | 227.8 (134-379) 9.9 (7.8-12.2) 35.4 28.9 37.5 11952 (7000-24000) | 214.8 (126-318) 10.7 (8.2-12.8) 29.1 23.6 37.4 13844 (7000-30000) | 214.8 (126-318) 10.7 (8.6-13.2) 14.2 16.9 24.3 11944 (5000-26000) | 217.6 (119-308) 10.8 (8.4-13.1) 20.1 13.4 22.1 13650 (9000-23000) | 0.896 0.020 0.022 0.049 0.251 0.203 | [†] Afib = atrial fibrillation; ASPItest = assay for determination of platelet function triggered by arachidonic acid; ADPtest = assay for determination of platelet function triggered by adenosine diphosphate; BMI = body mass index; MPV = mean platelet volume; PR = platelet reactivity; PVI = pulmonary vein isolation; TRAPtest = assay for determination of platelet function triggered by thrombin receptor activating peptide-6; UFH = unfractionated heparin FIGURE 1. Platelet reactivity change one day after pulmonary vein isolation in patients on different oral anticoagulation. ASPItest = assay for determination of platelet function triggered by arachidonic acid; ADPtest = assay for determination of platelet function triggered by adenosine diphosphate; VKA = vitamin K antagonist; TRAPtest = assay for determination of platelet function triggered by thrombin receptor activating peptide-6 **Conclusion**: Our results show that there is no significant effect of PVI on PR one day after the procedure regardless of chronic oral anticoagulation that was used. Lower basal PR was noted in patients on xabans compared to direct thrombin inhibitor and VKA. This antiplatelet mechanism is not fully understood but might be associated with multiple direct and indirect pathways which could contribute to potential differences in events between patients on certain DOACs. This warrants further investigation in seeking optimal DOAC choice for each patient. **Acknowledgement**: This study was part of SPARELIFE-CVD project funded by the Croatian Science Foundation.

    Literature

    1. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021 February 1;42(5):373–498. https://doi.org/10.1093/eurheartj/ehaa612
    2. Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2017 October;14(10):e275–444. https://doi.org/10.1016/j.hrthm.2017.05.012
    Cardiologia Croatica
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    Does platelet reactivity depend on chronic oral anticoagulation choice in patients undergoing pulmonary vein isolation?

    Extended Abstract
    Issue11-12
    Published
    Pages311-312
    PDF via DOIhttps://doi.org/10.15836/ccar2023.311
    direct oral anticoagulants
    vitamin K antagonists
    atrial fibrillation
    pulmonary vein isolation
    platelet reactivity

    Authors

    Petar SamardžićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Marijan PašalićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Laura RudeljORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Hrvoje JurinORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Ivo PlanincORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Maja ČikešORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Boško SkorićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Vedran VelagićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Jure Samardžić*ORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Davor MiličićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia

    *Correspondence email: jure.samardzic@gmail.com

    Full Text

    Introduction: Direct oral anticoagulants (DOACs) are recommended in preference to vitamin K antagonists (VKA) in patients with atrial fibrillation (Afib) (1). There is no direct comparison between DOACs and substantial share of patients are still treated with VKAs due to certain comorbidities or financial reasons. Pulmonary vein isolation (PVI) is an established procedure to treat paroxysmal and persistent Afib but it increases thromboembolic risk (2). The aim of this study was to compare periinterventional platelet reactivity (PR) in Afib patients undergoing PVI on different chronic oral anticoagulation.

    Patients and Methods: PR was analyzed with Multiplate function analyzer in 136 patients undergoing PVI procedures in our institution. Blood samples were drawn before the procedure and on the following morning. ASPItest, ADPtest and TRAPtest were used as assays for the quantitative in vitro determination of PR triggered by arachidonic acid, adenosine diphosphate and thrombin receptor activating peptide-6, respectively. Fourty three patients (31.6%) were taking VKA, while 38 (27.9%), 29 (21.3%) and 26 (19.1%) patients were treated with dabigatran, rivaroxaban and apixaban, respectively. Edoxaban was not available during the investigation.

    Results: There was no significant difference in demographics between the groups. Patients on VKA had lower mean platelet volume (MPV) compared to patients on DOACs (9.9 vs 10.7-10.8 fL; p=0.020). Patients on xabans (rivaroxaban and apixaban) had lower baseline PR compared to VKA and dabigatran (Table 1). One day after PVI, there was no significant change from PR baseline in all four groups (Figure 1).

    TABLE 1: Study patient characteristics.

    Age, years, mean (min-max)
    VKA (n=43)
    58.2 (36-73)
    Dabigatran (n=38)
    61.7 (45-76)
    Rivaroxaban (n=29)
    59.3 (42-77)
    Apixaban (n=26)
    60.1 (45-76)
    p
    0.659
    Men, n (%)
    VKA (n=43)
    31 (72.1)
    Dabigatran (n=38)
    27 (71.1)
    Rivaroxaban (n=29)
    22 (75.9)
    Apixaban (n=26)
    15 (57.7)
    p
    0.487
    BMI, kg/m2, mean (min-max) Paroxysmal Afib, n (%)
    VKA (n=43)
    29.2 (22.0-37.6) 32 (74.4)
    Dabigatran (n=38)
    28.96 (21.4-38.1) 31 (81.6)
    Rivaroxaban (n=29)
    27.68 (22.1-34.7) 20 (68.9)
    Apixaban (n=26)
    28.67 (23.1-38.3) 23 (88.5)
    p
    0.560 0.307
    Arterial hypertension, n (%) Hyperlipidemia, n (%)
    VKA (n=43)
    33 (76.7) 22 (51.2)
    Dabigatran (n=38)
    30 (78.9) 23 (60.5)
    Rivaroxaban (n=29)
    20 (68.9) 14 (48.3)
    Apixaban (n=26)
    24 (92.3) 12 (46.2)
    p
    0.206 0.654
    Diabetes mellitus, n (%) CrCl2DS2-VASc, mean (min-max) HAS-BLED, mean (min-max)
    VKA (n=43)
    1 (2.3) 2 (4.6) 1.72 (0-5) 0.77 (0-4)
    Dabigatran (n=38)
    3 (7.9) 6 (15.8) 1.94 (0-6) 1.12 (0-3)
    Rivaroxaban (n=29)
    4 (13.8) 4 (13.8) 2.07 (0-4) 1.00 (0-3)
    Apixaban (n=26)
    3 (11.5) 3 (11.5) 2.54 (0-5) 1.15 (0-4)
    p
    0.310 0.343 0.095 0.238
    Platelets, x109/L, mean (min-max) MPV, fL, mean (min-max) PR before PVI ASPItest, mean (U) ADPtest, mean (U) TRAPtest, mean (U) Periinterventional UFH administration, mean (IU) (min-max)
    VKA (n=43)
    227.8 (134-379) 9.9 (7.8-12.2) 35.4 28.9 37.5 11952 (7000-24000)
    Dabigatran (n=38)
    214.8 (126-318) 10.7 (8.2-12.8) 29.1 23.6 37.4 13844 (7000-30000)
    Rivaroxaban (n=29)
    214.8 (126-318) 10.7 (8.6-13.2) 14.2 16.9 24.3 11944 (5000-26000)
    Apixaban (n=26)
    217.6 (119-308) 10.8 (8.4-13.1) 20.1 13.4 22.1 13650 (9000-23000)
    p
    0.896 0.020 0.022 0.049 0.251 0.203

    Afib = atrial fibrillation; ASPItest = assay for determination of platelet function triggered by arachidonic acid; ADPtest = assay for determination of platelet function triggered by adenosine diphosphate; BMI = body mass index; MPV = mean platelet volume; PR = platelet reactivity; PVI = pulmonary vein isolation; TRAPtest = assay for determination of platelet function triggered by thrombin receptor activating peptide-6; UFH = unfractionated heparin

    FIGURE 1. Platelet reactivity change one day after pulmonary vein isolation in patients on different oral anticoagulation. ASPItest = assay for determination of platelet function triggered by arachidonic acid; ADPtest = assay for determination of platelet function triggered by adenosine diphosphate; VKA = vitamin K antagonist; TRAPtest = assay for determination of platelet function triggered by thrombin receptor activating peptide-6

    Conclusion: Our results show that there is no significant effect of PVI on PR one day after the procedure regardless of chronic oral anticoagulation that was used. Lower basal PR was noted in patients on xabans compared to direct thrombin inhibitor and VKA. This antiplatelet mechanism is not fully understood but might be associated with multiple direct and indirect pathways which could contribute to potential differences in events between patients on certain DOACs. This warrants further investigation in seeking optimal DOAC choice for each patient.

    Acknowledgement: This study was part of SPARELIFE-CVD project funded by the Croatian Science Foundation.

    Literature

    1. 1.
      Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021 February 1;42(5):373–498.DOI
    2. 2.
      Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2017 October;14(10):e275–444.DOI