Key result
Non-persistence with direct oral anticoagulants significantly increased the risk of ischaemic stroke compared to persistent use in patients with atrial fibrillation.
Why the study?
High adherence to DOACs is vital to reduce stroke risk in AF given rapid anticoagulant decline with omitted doses, but the impact of non-adherence and non-persistence on ischaemic stroke needed assessment.
Does non-adherence or non-persistence to direct oral anticoagulants increase the risk of ischaemic stroke in patients with atrial fibrillation?
Case-Control (n=12,798)
Yes
Does non-adherence or non-persistence to direct oral anticoagulants increase the risk of ischaemic stroke in patients with atrial fibrillation?
Non-persistence to direct oral anticoagulants significantly increases the risk of ischemic stroke in patients with atrial fibrillation in real-world settings.
Non-adherence to DOACs was associated with higher stroke risk in AF; leaves open whether adherence interventions reduce events.
BACKGROUND: A high degree of adherence to direct oral anticoagulants is essential for reducing the risk of ischaemic stroke and systemic embolism in patients with atrial fibrillation, owing to the rapid decline in anticoagulation activity when doses are omitted (i.e. rebound effect). OBJECTIVE: We aimed to assess the relationship between non-adherence and non-persistence with direct oral anticoagulants and the incidence of ischaemic stroke in patients with atrial fibrillation. The cohort entry date was the first dispensing date. Study patients were those aged ≥ 45 years, with ≥ 1 year database history, ≥ 1 year follow-up and at least two direct oral anticoagulant dispensings after the cohort entry date. Adherence and persistence to direct oral anticoagulant treatment were defined as the proportion of days covered ≥ 80% or direct oral anticoagulant continuous use between the cohort entry date and the index date (i.e. date of ischaemic stroke), respectively. RESULTS: In The Netherlands, Italy and Germany, 105 cases and 395 controls, 1580 cases and 6248 controls, and 900 cases and 3570 controls were included, respectively. Odds ratios (ORs) for stroke among current users who were non-adherent compared to adherent users were 0.43 (95% confidence interval [CI] 0.09-1.96) in The Netherlands, 1.11 (95% CI 0.98-1.26) in Italy and 1.21 (95% CI 1.01-1.45) in Germany. The risk of stroke was significantly higher among non-persistent users compared with persistent users in all three databases [OR 1.56 (95% CI 1.00-2.44), OR 1.48 (1.32-1.65) and OR 1.91 (95% CI 1.64-2.22), respectively]. In The Netherlands and Germany, the risk of stroke was higher the longer a patient had stopped using direct oral anticoagulants. CONCLUSIONS: Both non-adherence (in Germany) and non-persistence increased the risk of stroke, either using a once-daily or twice-daily regime.
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Holthuis et al. (2022) conducted a case-control in Atrial fibrillation (n=12,798). Non-adherence and non-persistence with direct oral anticoagulants vs. Adherent and persistent DOAC users was evaluated on Ischaemic stroke (non-persistence vs persistence in Italy cohort) (OR 1.48, 95% CI 1.32-1.65, p=<0.05). Non-persistence with direct oral anticoagulants significantly increased the risk of ischaemic stroke compared to persistent use in patients with atrial fibrillation.
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