CC BY 4.0 · Thromb Haemost 2024; 124(08): 778-790
DOI: 10.1055/a-2168-9378
Stroke, Systemic or Venous Thromboembolism

Effect of Previous INR Control during VKA Therapy on Subsequent DOAC Adherence and Persistence, in Patients Switched from VKA to DOAC

1   Department of Hematology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
,
Eelko Hak
2   Groningen Research Institute of Pharmacy, Unit of Pharmacotherapy, Epidemiology and Economy, University of Groningen, Groningen, The Netherlands
,
Jens H. Bos
2   Groningen Research Institute of Pharmacy, Unit of Pharmacotherapy, Epidemiology and Economy, University of Groningen, Groningen, The Netherlands
,
Vladimir Y. I. G. Tichelaar
1   Department of Hematology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
3   Certe Thrombosis Service, Groningen, The Netherlands
,
Nic J. G. M. Veeger
4   Department of Epidemiology, University of Groningen, University Medical Centre, Groningen, The Netherlands
,
Karina Meijer
1   Department of Hematology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
› Author Affiliations


Abstract

Introduction Current guideline suggests a switch from vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) in patients with low time in therapeutic range (TTR < 70%). Poor international normalized ratio (INR) control may be the result of poor compliance, and might therefore be associated with subsequent DOAC intake. Therefore, this study evaluates the effect of previous TTR and other measures of INR control on DOAC nonadherence and nonpersistence, in patients who switched from VKA to DOAC.

Methods A total of 437 patients who switched from VKA to DOAC between 2012 and 2019 were included using data from Certe Thrombosis Service, IADB.nl pharmacy community database University Groningen, and Statistics Netherlands. DOAC prescriptions were used to determine nonadherence and nonpersistence. INR control (i.e., TTR, time under therapeutic range [TUR], and INR variability) was assessed during the last 180 days of VKA use. Multivariable regression models were applied to determine the association between INR control and DOAC nonpersistence/nonadherence.

Results On VKA, 67.7% of the patients had a TTR below 70%. DOAC nonpersistence was 39.8% (95% confidence interval [CI]: 33.4–45.5%) during a median follow-up of 34.4 months (interquartile range: 19.1–49.2). Approximately 80% of persistent patients were DOAC-adherent. Low TTR was not associated with DOAC nonpersistence (hazard ratio: 1.14, 95% CI: 0.69–1.87) and DOAC nonadherence (odds ratio: 1.38, 95% CI: 0.67–2.84), nor were TUR and INR variability.

Conclusion Previous INR control during VKA therapy is not associated with subsequent DOAC nonadherence and nonpersistence. This study suggests that INR control on VKA cannot, and therefore should not, be used for predicting DOAC adherence or persistence.

Supplementary Material



Publication History

Received: 25 April 2023

Accepted: 03 September 2023

Accepted Manuscript online:
06 September 2023

Article published online:
09 October 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Hindricks G, Potpara T, Dagres N. et al; ESC Scientific Document Group. 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; 42 (05) 373-498
  • 2 Streiff MB, Agnelli G, Connors JM. et al. Guidance for the treatment of deep vein thrombosis and pulmonary embolism. J Thromb Thrombolysis 2016; 41 (01) 32-67
  • 3 Ozaki AF, Choi AS, Le QT. et al. Real-world adherence and persistence to direct oral anticoagulants in patients with atrial fibrillation: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes 2020; 13 (03) e005969
  • 4 Banerjee A, Benedetto V, Gichuru P. et al. Adherence and persistence to direct oral anticoagulants in atrial fibrillation: a population-based study. Heart 2020; 106 (02) 119-126
  • 5 Yagi N, Suzuki S, Nagai K. et al. Current status of oral anticoagulant adherence in Japanese patients with atrial fibrillation: a claims database analysis. J Cardiol 2021; 78 (02) 150-156
  • 6 Zielinski GD, van Rein N, Teichert M. et al. Adherence to direct oral anticoagulant treatment for atrial fibrillation in the Netherlands: a surveillance study. Pharmacoepidemiol Drug Saf 2021; 30 (08) 1027-1036
  • 7 Pundi KN, Perino AC, Fan J. et al. Direct oral anticoagulant adherence of patients with atrial fibrillation transitioned from warfarin. J Am Heart Assoc 2021; 10 (23) e020904
  • 8 Packard A, Delate T, Martinez K, Clark NP. Adherence to and persistence with direct oral anticoagulant therapy among patients with new onset venous thromboembolism receiving extended anticoagulant therapy and followed by a centralized anticoagulation service. Thromb Res 2020; 193: 40-44
  • 9 Borne RT, O'Donnell C, Turakhia MP. et al. Adherence and outcomes to direct oral anticoagulants among patients with atrial fibrillation: findings from the veterans health administration. BMC Cardiovasc Disord 2017; 17 (01) 236
  • 10 Toorop MMA, Chen Q, Tichelaar VYIG, Cannegieter SC, Lijfering WM. Predictors, time course, and outcomes of persistence patterns in oral anticoagulation for non-valvular atrial fibrillation: a Dutch Nationwide Cohort Study. Eur Heart J 2021; 42 (40) 4126-4137
  • 11 Sediq R, van der Schans J, Dotinga A. et al. Concordance assessment of self-reported medication use in the Netherlands three-generation Lifelines Cohort study with the pharmacy database iaDB.nl: the PharmLines initiative. Clin Epidemiol 2018; 10: 981-989
  • 12 Rosendaal FR, Cannegieter SC, van der Meer FJ, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993; 69 (03) 236-239
  • 13 Fihn SD, McDonell M, Martin D. et al; Warfarin Optimized Outpatient Follow-up Study Group. Risk factors for complications of chronic anticoagulation. A multicenter study. Ann Intern Med 1993; 118 (07) 511-520
  • 14 Vestergaard AS, Skjøth F, Larsen TB, Ehlers LH. The importance of mean time in therapeutic range for complication rates in warfarin therapy of patients with atrial fibrillation: a systematic review and meta-regression analysis. PLoS One 2017; 12 (11) e0188482
  • 15 Veeger NJ, Piersma-Wichers M, Tijssen JG, Hillege HL, van der Meer J. Individual time within target range in patients treated with vitamin K antagonists: main determinant of quality of anticoagulation and predictor of clinical outcome. A retrospective study of 2300 consecutive patients with venous thromboembolism. Br J Haematol 2005; 128 (04) 513-519
  • 16 Björck F, Renlund H, Lip GY, Wester P, Svensson PJ, Själander A. Outcomes in a warfarin-treated population with atrial fibrillation. JAMA Cardiol 2016; 1 (02) 172-180
  • 17 van Leeuwen Y, Rosendaal FR, Cannegieter SC. Prediction of hemorrhagic and thrombotic events in patients with mechanical heart valve prostheses treated with oral anticoagulants. J Thromb Haemost 2008; 6 (03) 451-456
  • 18 Alfian SD, Pradipta IS, Hak E, Denig P. A systematic review finds inconsistency in the measures used to estimate adherence and persistence to multiple cardiometabolic medications. J Clin Epidemiol 2019; 108: 44-53
  • 19 Bijlsma MJ, Janssen F, Hak E. Estimating time-varying drug adherence using electronic records: extending the proportion of days covered (PDC) method. Pharmacoepidemiol Drug Saf 2016; 25 (03) 325-332
  • 20 Manzoor BS, Lee TA, Sharp LK, Walton SM, Galanter WL, Nutescu EA. Real-world adherence and persistence with direct oral anticoagulants in adults with atrial fibrillation. Pharmacotherapy 2017; 37 (10) 1221-1230
  • 21 Zielinski GD, van Rein N, Teichert M. et al. Persistence of oral anticoagulant treatment for atrial fibrillation in the Netherlands: a surveillance study. Res Pract Thromb Haemost 2019; 4 (01) 141-153
  • 22 Dronkers CEA, Lijfering WM, Teichert M. et al. Persistence to direct oral anticoagulants for acute venous thromboembolism. Thromb Res 2018; 167: 135-141
  • 23 Patel SM, Wang T, Outler DL. et al. Low persistence to rivaroxaban or warfarin among patients with new venous thromboembolism at a safety net academic medical center. J Thromb Thrombolysis 2020; 49 (02) 287-293
  • 24 Toorop MMA, Chen Q, Kruip MJHA. et al. Switching from vitamin K antagonists to direct oral anticoagulants in non-valvular atrial fibrillation patients: does low time in therapeutic range affect persistence?. J Thromb Haemost 2022; 20 (02) 339-352
  • 25 Ording AG, Søgaard M, Nielsen PB. et al. Oral anti-coagulant treatment patterns in atrial fibrillation patients diagnosed with cancer: a Danish nationwide cohort study. Br J Haematol 2022; 197 (02) 223-231
  • 26 Schaefer JK, Li M, Wu Z. et al. Anticoagulant medication adherence for cancer-associated thrombosis: a comparison of LMWH to DOACs. J Thromb Haemost 2021; 19 (01) 212-220
  • 27 Granger CB, Alexander JH, McMurray JJ. et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365 (11) 981-992
  • 28 Connolly SJ, Ezekowitz MD, Yusuf S. et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361 (12) 1139-1151
  • 29 Patel MR, Mahaffey KW, Garg J. et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365 (10) 883-891
  • 30 Mitrovic D, Folkeringa R, Veeger N, van Roon E. Reasons for discontinuation of novel oral anticoagulant therapy in patients with atrial fibrillation. Curr Med Res Opin 2020; 36 (04) 547-553
  • 31 Visser ST, Schuiling-Veninga CC, Bos JH, de Jong-van den Berg LT, Postma MJ. The population-based prescription database IADB.nl: its development, usefulness in outcomes research and challenges. Expert Rev Pharmacoecon Outcomes Res 2013; 13 (03) 285-292