Is it safe to start dabigatran in the first days after ischemic stroke?
For patients after cardioembolic ischemic stroke (iCMP), starting anticoagulant therapy is crucial, but it is not strictly defined how many days after iCMP it is ideal to begin. The article provides a summary of a recent observational study that investigated the appropriate timing of starting dabigatran in patients with non-valvular atrial fibrillation (NVAF) after their first iCMP who were treated with intravenous thrombolysis or endovascular thrombectomy.
Introduction
The risk of recurrent cardioembolic iCMP during the first 14 days without anticoagulant therapy is around 5%. With heparin anticoagulation, the risk of another iCMP decreases to 3%, but the occurrence of intracranial hemorrhage (ICH) increases to 1.8%. Anticoagulant therapy with direct oral anticoagulants (DOACs) reduces the risk of recurrent iCMP to 2.8% over 90 days. For doctors, a crucial question is when to start anticoagulant therapy in secondary prevention due to the existing risk of ICH.
Recommendations and previous studies
National and international guidelines for stroke treatment are not strict regarding the initiation of oral anticoagulation (OAC). The AHA/ASA (American Heart Association/American Stroke Association) 2018 guidelines state that for most patients, it is appropriate within 4–14 days after acute iCMP, and the ESC (European Society of Cardiology) 2016 and EHRA (European Heart Rhythm Association) 2018 guidelines recommend initiating OAC 1, 3, 6, or 12 days after a transient ischemic attack, mild, moderate, and severe stroke, respectively. In clinical practice, however, anticoagulant therapy is often initiated even after more than 14 days.
Recently conducted observational studies have suggested that the risk of symptomatic ICH in patients treated with DOACs within the first 5 days after iCMP is low. According to an analysis of pooled data from 7 observational studies, early initiation of DOACs after iCMP is associated with a lower risk of adverse clinical outcomes compared to vitamin K antagonists, mainly due to a lower risk of ICH.
Evaluated patient population
The retrospective observational study included adult patients with NVAF enrolled in the SITS-AF (Safe Implementation of treatment in Stroke – Atrial Fibrillation) registry between July 2014 and July 2018, who were diagnosed with their first iCMP subsequently treated with intravenous thrombolysis (IVT) with alteplase, endovascular thrombectomy (EVT), or both methods, and were started on dabigatran from the DOACs group within 3 months. Besides the ideal timing of dabigatran initiation, the authors also examined the reasons for delaying this treatment until after discharge from acute hospital care and assessed clinical outcomes at a 3-month follow-up post-iCMP.
The primary monitored parameter was the time between iCMP and dabigatran initiation. The authors had data from 1240 patients with the following baseline characteristics: average age 75 years, 53% women, 15% on OAC, 29% on acetylsalicylic acid, and 4% on clopidogrel, with an average NIHSS score at admission of 10.
Results
In 82% of patients, dabigatran therapy was initiated within the first 14 days after iCMP. The average time between iCMP and dabigatran initiation was 8 days (4–12). Dabigatran was initiated earlier (7–15 days) in patients with milder iCMP (NIHSS 6–13, median 8) compared to later initiation (after 28 days up to 3 months) in patients with a more severe course (NIHSS 9–19, median 15).
Data on the reasons for delaying dabigatran treatment were known for 203 patients. In 65.3% of cases, it was due to the severity of the stroke, its hemorrhagic transformation, intracranial hemorrhage, and the extent of the infarct. During the first 3 months after iCMP, out of 926 patients whose information was obtained, 20 (2.2%) experienced a thrombotic or hemorrhagic event (new stroke, acute myocardial infarction, pulmonary embolism, or systemic embolism, intracranial or major extracranial bleeding).
Summary and conclusion
The results of the retrospective analysis indicate that doctors usually start dabigatran therapy within the first days after iCMP, and the incidence of hemorrhagic or ischemic complications is low in the subsequent 3 months. The study suggests that early initiation of dabigatran in secondary prevention is safe for patients treated with IVT, EVT, or both methods.
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Source:
Escudero-Martinez I., Mazya M., Teutsch C. et al. Dabigatran initiation in patients with non-valvular AF and first acute ischaemic stroke: a retrospective observational study from the SITS registry. BMJ Open 2020; 10 (5): e037234, doi: 10.1136/bmjopen-2020-037234.
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