Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation

Abstract

Background and Purpose— The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods— The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results— Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA 2 DS 2 -VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30–0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively ( P =0.003). Conclusions— Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA 2 DS 2 -VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non–Vitamin‐K Oral Anticoagulants (RAF‐NOACs) Study

“…Thus, such a decision hinges on the assessment of the competing risks of early thromboembolic recurrences and hemorrhagic transformation 3. Data from the RAF (Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation) study suggested that the optimal time for initiating anticoagulation treatment for secondary stroke prevention may be 4 to 14 days from stroke onset 4. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low‐molecular‐weight heparins (LMWHs) alone or before oral anticoagulants.…”

“…Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low‐molecular‐weight heparins (LMWHs) alone or before oral anticoagulants. In the RAF study, with enrollment from January 2012 to March 2014, <10% of the patients were treated with non–vitamin K oral anticoagulants (NOACs) 4. Observational studies reported that, if NOACs are started early after an index event, the risk of intracranial bleeding appears to be low 5, 6, 7…”

Early Anticoagulation for Recurrent Ischemic Stroke despite the Presence of Ventricular Bleeding

“…As advanced age is not a contraindication to the use of rivaroxaban [14], he was treated with this DOAC at the dose of 15 mg/die starting 5 days after the index event, despite the presence of intraventricular bleeding occurred after the thrombolytic therapy for the first event. Our results are even more encouraging given that randomized clinical trials with DOACs have excluded acute ischemic stroke patients, and the safety of DOAC administration soon after an index event has only been addressed by observational, prospective, and non-randomized studies [8][9][10][11][12][13]. In particular, in two prospective studies, the treatment with DOACs was commenced after a mean time of four and five days from the index event and no intracranial bleeding was observed during hospitalization [8,13], suggesting the safety of the early use of DOACs after an ischemic episode.…”

“…However, randomized clinical trials on DOACs have systematically excluded patients with recent ischemic stroke (<7 days) in whom the risk of sHT is higher [4][5][6][7]. Despite the lack of conclusive clinical evidence, the available data from observational, longitudinal studies suggest that the early use of DOACs is safe and might reduce the risk of sHT [8][9][10][11][12][13]. Therefore, in clinical practice, these agents are perceived as safe and increasingly used even during the first days after ischemic stroke.…”

THE EFFICACY OF LONG-TERM WARFARIN THERAPY: THE IMPACT ON THE INCIDENCE OF ISCHEMIC CEREBROVASCULAR DISORDERS AND CLINICAL PREDICTORS OF DEVELOPING SUCH DISORDERS. (Results of a prospective 10-year follow-up study)

“…Однако при от-дельной оценке данной группы пациентов бы-ло выявлено, что повторные НМК у этой кате-гории за 10 лет наблюдения были отмечены у 28,6%. Перенесенный инсульт в анамнезе явля-ется независимым фактором риска повторных НМК [1][2][3]19] Так, по данным работ, посвя-щенных краткосрочному прогнозу больных с ФП, перенесших острый инсульт, выявлено, что частота повторных инсультов достигает 7,6-10% в течение 90 дней [6,[20][21]. Среди наших 49 пациентов, перенесших инсульты до момента включения в исследование, у 20 (40,8%) инсульт произошел в течение послед-него года, что делает этих пациентов наиболее уязвимыми в отношении повторных мозговых катастроф.…”