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Non-Persistence to Direct Oral Anticoagulants and Risk of Thromboembolic Stroke among Patients with Non-Valvular Atrial Fibrillation: A Dutch Nationwide Cohort Study

M.M.A. Toorop1, Q. Chen1, V. Tichelaar2, S.C. Cannegieter1, W.M. Lijfering1

1Leiden University Medical Center, Clinical Epidemiology, Leiden, the Netherlands, 2University Medical Center Groningen, Department of Hematology, Groningen, the Netherlands

Abstract Number: PB2047

Meeting: ISTH 2020 Congress

Theme: Venous Thromboembolism and Cardioembolism » Atrial Fibrillation

Background: Direct oral anticoagulants (DOACs) are used for thromboembolic stroke prevention in patients with non-valvular atrial fibrillation (AF), but their effectiveness is expected to depend on drug persistence.

Aims: To study the association between non-persistence to DOACs and thromboembolic stroke risk among AF patients.

Methods: With nationwide statistics we identified and followed all AF patients who started DOAC treatment between January 2013-September 2017. Non-persistence was defined according to the last DOAC prescription during follow-up, using a 100-day gap and allowing a switch to vitamin K antagonists. With time-dependent Cox modelling, we estimated the risk of thromboembolic stroke/death due to ischemic stroke (composite outcome) associated with non-persistence. Adjustments were made for age, sex, VKA history, stroke history, AF type, and household income. In addition, a stratified analysis based on CHA2DS2-VASc >2 was performed. According to guidelines, AF patients with a score of < 2 who are converted to sinus rhythm may discontinue anticoagulation contrary to those with high CHA2DS2-VASc scores.

Results: 70574 incident DOAC users with AF were included; mean age was 71.4 years, 57%(n=40318) were men and 49%(n=34272) had a CHA2DS2-VASc >2. The cumulative incidence of non-persistence was 42% at 4 years follow-up and the overall incidence of the composite outcome was 1.08% (95%CI,1.01-1.14) per year. The adjusted hazard ratio [AHR] for the composite outcome was 1.69 (95%CI,1.31-2.18) for those who were non-persistent to DOAC (Table). Subgroup analyses suggested that those with CHA2DS2-VASc 0-2 who were non-persistent had a lower risk of the composite outcome (HR 0.71; 95%CI,0.48-1.04) compared to persistent patients. However, patients with CHA2DS2-VASc >2 who were non-persistent to DOAC had high risks of the composite outcome, compared to persistent patients (HR 2.51; 95%CI,1.87-3.35 and 2.46;1.76-3.42, for CHA2DS2-VASc score 3-4 and CHA2DS2-VASc score >5, respectively).

Conclusions: Non-persistence to DOAC was associated with an increased risk of thromboembolic stroke in Dutch non-valvular AF patients.

  Observation years No. of events adjusted HR (95%CI) (age and sex) adjusted HR (95%CI) (all variables) HR (95%CI); CHA2DS2-VASc 0-2 HR (95%CI); CHA2DS2-VASc 3-4 HR (95%CI); CHA2DS2-VASc ≥ 5
Persistent 96789 1037 1 (reference) 1 (reference) 1 (reference) 1 (reference) 1 (reference)
Non-persistent 10982 123 1.64 (1.36-1.98) 1.69 (1.31-2.18) 0.71 (0.48-1.04) 2.51 (1.87-3.35) 2.46 (1.76-3.42)

[Table 1. Non-persistence to DOAC in relation to the composite outcome (ischemic stroke and ischemic stroke-related mortality)]

To cite this abstract in AMA style:

Toorop MMA, Chen Q, Tichelaar V, Cannegieter SC, Lijfering WM. Non-Persistence to Direct Oral Anticoagulants and Risk of Thromboembolic Stroke among Patients with Non-Valvular Atrial Fibrillation: A Dutch Nationwide Cohort Study [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/non-persistence-to-direct-oral-anticoagulants-and-risk-of-thromboembolic-stroke-among-patients-with-non-valvular-atrial-fibrillation-a-dutch-nationwide-cohort-study/. Accessed September 24, 2023.

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