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Persistence Pattern to Oral Anticoagulants among Non-valvular Atrial Fibrillation Patients who Switched from Vitamin K Antagonists to Direct Oral Anticoagulants: A Cohort Study

M.M. Toorop1, Q. Chen1, M.J. Kruip2,3, F.J. van der Meer1, M. Nierman4, L. Faber5, L. Goede6, S.C. Cannegieter1, W.M. Lijfering1

1Leiden University Medical Center, Leiden, Netherlands, 2Erasmus University Medical Center, Rotterdam, Netherlands, 3Thrombosis Service Star-shl, Rotterdam, Netherlands, 4Thrombosis Service Atalmedial, Amsterdam, Netherlands, 5Red Cross Hospital, Beverwijk, Netherlands, 6Thrombosis Service Saltro, Utrecht, Netherlands

Abstract Number: LPB0003

Meeting: ISTH 2021 Congress

Theme: Arterial Thromboembolism » Cerebrovascular Disorders

Background: Patients with non-valvular atrial fibrillation (NVAF) who use vitamin K antagonist (VKA) and have low Time in Therapeutic Range (TTR) should switch to direct oral anticoagulants (DOAC) according to international guidelines.

Aims: To determine if patients on VKA with a low TTR who are switched to DOAC have a same persistence rate to oral anticoagulants (OAC) as patients on VKA with a high TTR who are also switched to DOAC.

Methods: Individual data was obtained from anticoagulation clinics and Statistic Netherlands. Adult NVAF patients who were switched from VKA to DOAC between April-2013 and September-2018 were stratified by baseline TTR and followed from the date of switch. OAC prescription records were examined to determine non-persistence, based on a 100-day gap. Cumulative incidences of non-persistence to OAC (allowing a switch back to VKA) and DOAC (not allowing a switch back to VKA) after 6 months, 1 and 4 years of follow-up were estimated and multivariable Cox regression models were employed to evaluate the associations of baseline TTR with OAC non-persistence.

Results:

Non-persistent to all OAC (allowing a switch back to VKA) Non-persistent to DOAC (not allowing a switch back to VKA)
Time since switch to DOAC Follow-up (years) No. at risk No. event Cumulative incidence (95%CI) (%) * Follow-up (years) No. at risk No. event Cumulative incidence (95%CI) (%) *
TTR≤45%
0-6 months 483.83 1132 43 4.12 (3.03-5.45) 466.82 1132 91 8.59 (7-10.38)
0-1 year 857.31 1132 80 8.52 (6.83-10.43) 819.23 1132 133 13.58 (11.49-15.83)
0-4 year 1697.32 1132 141 24.06 (19.63-28.75) 1584.05 1132 195 29.69 (24.91-34.62)
TTR>45%
0-6 months 1335.69 2968 81 2.87 (2.3-3.54) 1291.54 2968 195 6.83 (5.94-7.8)
0-1 year 2434.01 2968 124 4.69 (3.92-5.54) 2332.42 2968 256 9.42 (8.35-10.56)
0-4 year 5518.46 2968 267 16.16 (14.13-18.31) 5185.26 2968 389 20.26 (18.15-22.45)
* estimated by cumulative incidence competing risk (CICR) method.
Abbreviations: OAC, oral anticoagulants; DOAC, direct oral anticoagulants; VKA, Vitamin K antagonists; CI, confidence interval; TTR, time in therapeutic range

Table 1 Cumulative incidences of non-persistence to OAC and DOAC, stratified by baseline TTR

Observation time (person-year) No. event Incidence rate (95%CI) (per 100-person year) HR (95%CI) HR* (95%CI) HR† (95%CI) HR†‡ (95%CI)
TTR>45% 5735.75 290 5.06 (4.49-5.67) 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
TTR≤45% 1736.54 144 8.29 (6.99-9.76) 1.64 (1.34-2.01) 1.66 (1.35-2.03) 1.63 (1.32-2) 1.49 (1.17-1.9)
TTR>60% 4564.35 213 4.67 (4.06-5.34) 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
TTR≤60% 2907.94 221 7.6 (6.63-8.67) 1.6 (1.28-2) 1.59 (1.27-2) 1.55 (1.23-1.95) 1.55 (1.23-1.95)
TTR>70% 3656.69 169 4.62 (3.95-5.37) 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
TTR≤70% 3815.61 265 6.95 (6.13-7.83) 1.52 (1.21-1.92) 1.51 (1.19-1.91) 1.47 (1.16-1.87) 1.47 (1.16-1.87)
Notes: * Adjusted for age, sex, and anticoagulation clinics.
† Adjusted for age, sex, anticoagulation clinics, and comorbidities (chronic obstructive pulmonary disease, asthma, other chronic lung diseases, congestive heart failure, hypertension, myocardial infarction history, abnormal liver function, gastroesophageal reflux disease, peptic ulcer disease, abnormal renal function, anemia, coagulopathy, diabetes mellitus, thyroid disease, autoimmune disease, systemic connective tissue disorders, stroke/TIA history, Alzheimer’s disease, Parkinson’s disease, peripheral artery disease, deep vein thrombosis, pulmonary embolism, arterial embolism and thrombosis, major bleeding history, malignant tumor).
‡ Restricted to patients who had a baseline CHA2DS2-VASc ≥ 2.
Abbreviations: DOAC, direct oral anticoagulants; OAC, oral anticoagulants; TTR, time in therapeutic range; VKA, Vitamin K antagonists; HR, hazard ratio; CI, confidence interval.

Table 2 Risk of non-persistence to OAC between different levels of TTR during VKA treatment
4100 patients were included of which 28% had a baseline TTR≤45%. 8.5% (95%CI 6.8-10.4) of patients with a baseline TTR≤45% were non-persistent to OAC at 1 year after the switch compared to 4.7% (95%CI 3.9-5.5) of patients with a baseline TTR >45% (Table 1). After adjustments for age, sex, anticoagulation clinics, and comorbidities, a baseline TTR ≤45% was associated with a higher risk of non-persistence to OAC (Hazard ratio 1.63, 95%CI 1.35-2.03) when compared to TTR>45% (Table 2). This trend was similar when using other cut-off points for baseline TTR (60%;70%).

Conclusions: For NVAF patients who switched from VKA to DOAC, a low baseline TTR was associated with an increased risk of being non-persistent to OAC. Clinicians should consider this risk before switching a patient from VKA to DOAC.

To cite this abstract in AMA style:

Toorop MM, Chen Q, Kruip MJ, van der Meer FJ, Nierman M, Faber L, Goede L, Cannegieter SC, Lijfering WM. Persistence Pattern to Oral Anticoagulants among Non-valvular Atrial Fibrillation Patients who Switched from Vitamin K Antagonists to Direct Oral Anticoagulants: A Cohort Study [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/persistence-pattern-to-oral-anticoagulants-among-non-valvular-atrial-fibrillation-patients-who-switched-from-vitamin-k-antagonists-to-direct-oral-anticoagulants-a-cohort-study/. Accessed September 22, 2023.

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