Sophie Testa1, Armando Tripodi2, Cristina Legnani3, Vittorio Pengo4, Rosanna Abbate5, Claudia Dellanoce6, Paolo Carraro7, Luisa Salomone3, Rita Paniccia5, Oriana Paoletti6, Daniela Poli7, Gualtiero Palareti8. 1. Haemostasis and Thrombosis Center, Department of Laboratory Medicine, AO Istituti Ospitalieri, Cremona, Italy. Electronic address: s.testa@ospedale.cremona.it. 2. Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy. 3. Angiology and Blood Coagulation, University Hospital of Bologna, Italy. 4. Department of Cardiothoracic and Vascular Sciences, University Hospital of Padua, Padua, Italy. 5. Thrombosis Centre, Department of Heart and Vessels, University Hospital of Florence, Florence, Italy. 6. Haemostasis and Thrombosis Center, Department of Laboratory Medicine, AO Istituti Ospitalieri, Cremona, Italy. 7. Department of Laboratory Medicine, ULSS 16 and University-Hospital of Padova. 8. Cardiovascular Diseases, University of Bologna, Bologna, Italy.
Abstract
INTRODUCTION: Direct oral anticoagulant (DOAC) intra- and inter-individual variability was previously reported, but its magnitude is still considered negligible for patient management. OBJECTIVE: To evaluate inter- and intra-individual variability in real-world atrial fibrillation patients on dabigatran, rivaroxaban or apixaban in four Italian anticoagulation clinics and to assess the correlation between DOAC plasma concentration and creatinine-clearance (CrCl). MATERIALS AND METHODS: A total of 330 consecutive patients were enrolled, of which 160 were on dabigatran (70 and 90 taking 150 mg or 110 mg twice-daily, respectively), 71 on rivaroxaban (37 and 34 taking 20mg or 15 mg once-daily) and 99 on apixaban (73 and 26 taking 5mg or 2.5mg twice-daily). Blood was taken at trough and peak within the first month (15-25 days) of treatment. Diluted-thrombin-time (dTT) calibrated for dabigatran and anti-FXa calibrated for rivaroxaban or apixaban was performed. RESULTS: Mean inter-individual variability expressed as overall CV values for all drugs was lower at peak (CV=46%) than at trough (CV=63%). Mean CV% intra-individual variability was 36.6% at trough and 34.0% at peak. Correlation with CrCl was poor for all drugs and only dabigatran at trough showed a significant correlation. CONCLUSION: This multicenter study confirms high DOAC inter-individual variability that cannot be explained by the rate of renal clearance to which the three DOAC were subjected since the correlation with CrCl was relatively poor. This poor correlation suggests caution in using CrCl as the sole laboratory parameter to indirectly evaluate residual circulating DOAC.
INTRODUCTION: Direct oral anticoagulant (DOAC) intra- and inter-individual variability was previously reported, but its magnitude is still considered negligible for patient management. OBJECTIVE: To evaluate inter- and intra-individual variability in real-world atrial fibrillationpatients on dabigatran, rivaroxaban or apixaban in four Italian anticoagulation clinics and to assess the correlation between DOAC plasma concentration and creatinine-clearance (CrCl). MATERIALS AND METHODS: A total of 330 consecutive patients were enrolled, of which 160 were on dabigatran (70 and 90 taking 150 mg or 110 mg twice-daily, respectively), 71 on rivaroxaban (37 and 34 taking 20mg or 15 mg once-daily) and 99 on apixaban (73 and 26 taking 5mg or 2.5mg twice-daily). Blood was taken at trough and peak within the first month (15-25 days) of treatment. Diluted-thrombin-time (dTT) calibrated for dabigatran and anti-FXa calibrated for rivaroxaban or apixaban was performed. RESULTS: Mean inter-individual variability expressed as overall CV values for all drugs was lower at peak (CV=46%) than at trough (CV=63%). Mean CV% intra-individual variability was 36.6% at trough and 34.0% at peak. Correlation with CrCl was poor for all drugs and only dabigatran at trough showed a significant correlation. CONCLUSION: This multicenter study confirms high DOAC inter-individual variability that cannot be explained by the rate of renal clearance to which the three DOAC were subjected since the correlation with CrCl was relatively poor. This poor correlation suggests caution in using CrCl as the sole laboratory parameter to indirectly evaluate residual circulating DOAC.
Authors: E Chaussade; O Hanon; C Boully; F Labourée; L Caillard; G Gerotziafas; J-S Vidal; I Elalamy Journal: J Nutr Health Aging Date: 2018 Impact factor: 4.075
Authors: Markus Gulilat; Denise Keller; Bradley Linton; A Demetri Pananos; Daniel Lizotte; George K Dresser; Jeffrey Alfonsi; Rommel G Tirona; Richard B Kim; Ute I Schwarz Journal: J Thromb Thrombolysis Date: 2020-02 Impact factor: 2.300