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

Background The optimal timing to administer non–vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention. Methods and Results Recurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA 2 DS 2‐VASc score >4 and less reduced renal function. Thirty‐two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated >14 days after acute stroke. Conclusions In patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days.

[1]  Correction to: 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. , 2018, Stroke.

[2]  G. D. De Marchis,et al.  Author response: Early start of DOAC after ischemic stroke: Risk of intracranial hemorrhage and recurrent events , 2017, Neurology.

[3]  M. Campbell What is propensity score modelling? , 2017, Emergency Medicine Journal.

[4]  G. D. De Marchis,et al.  Early start of DOAC after ischemic stroke , 2016, Neurology.

[5]  W. Ageno,et al.  Timing of anticoagulation therapy in patients with acute ischaemic stroke and atrial fibrillation , 2016, Thrombosis and Haemostasis.

[6]  M. Kate,et al.  Early Rivaroxaban Use After Cardioembolic Stroke May Not Result in Hemorrhagic Transformation: A Prospective Magnetic Resonance Imaging Study , 2016, Stroke.

[7]  K. Kario,et al.  Three-month risk-benefit profile of anticoagulation after stroke with atrial fibrillation: The SAMURAI-Nonvalvular Atrial Fibrillation (NVAF) study , 2016, International journal of stroke : official journal of the International Stroke Society.

[8]  W. Ageno,et al.  Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing The RAF Study , 2015, Stroke.

[9]  V. Caso,et al.  Association of improved outcome in acute ischaemic stroke patients with atrial fibrillation who receive early antithrombotic therapy: analysis from VISTA , 2015, European journal of neurology.

[10]  Christopher S Coffey,et al.  2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association , 2015, Stroke.

[11]  M. Ezekowitz,et al.  2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. , 2014, Circulation.

[12]  Z. Ademi,et al.  Overview of methods for comparing the efficacies of drugs in the absence of head‐to‐head clinical trial data , 2014, British journal of clinical pharmacology.

[13]  M. Wintermark,et al.  Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association , 2013, Stroke.

[14]  G. Reboldi,et al.  Multivariable Analysis in Cerebrovascular Research: Practical Notes for the Clinician , 2013, Cerebrovascular Diseases.

[15]  Long-term risk of dementia after TIA and stroke: current estimates from a large population-based study , 2013 .

[16]  J. Bogousslavsky,et al.  Stroke Syndromes: Arterial territories of the human brain , 2001 .

[17]  D. Atar,et al.  Apixaban versus warfarin in patients with atrial fibrillation. , 2011, The New England journal of medicine.

[18]  R. Troughton,et al.  Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. , 2011, The New England journal of medicine.

[19]  Gregory Y H Lip,et al.  Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. , 2010, Chest.

[20]  D Bergqvist,et al.  Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients , 2010, Journal of thrombosis and haemostasis : JTH.

[21]  S. Yusuf,et al.  Dabigatran versus warfarin in patients with atrial fibrillation. , 2009, The New England journal of medicine.

[22]  Uwe Siebert,et al.  Good research practices for comparative effectiveness research: approaches to mitigate bias and confounding in the design of nonrandomized studies of treatment effects using secondary data sources: the International Society for Pharmacoeconomics and Outcomes Research Good Research Practices for Retr , 2009, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[23]  M. Kaste,et al.  Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. , 2008, The New England journal of medicine.

[24]  Giancarlo Comi,et al.  Early Hemorrhagic Transformation of Brain Infarction: Rate, Predictive Factors, and Influence on Clinical Outcome: Results of a Prospective Multicenter Study , 2008, Stroke.

[25]  Gary A. Ford,et al.  Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. , 2008, Cerebrovascular diseases.

[26]  John P.A. Ioannidis,et al.  Comparison of evidence on harms of medical interventions in randomized and nonrandomized studies , 2006, Canadian Medical Association Journal.

[27]  S. Schulman,et al.  Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non‐surgical patients , 2005, Journal of thrombosis and haemostasis : JTH.

[28]  P. Scheltens,et al.  A New Rating Scale for Age-Related White Matter Changes Applicable to MRI and CT , 2001, Stroke.

[29]  J. Bogousslavsky,et al.  Arterial territories of human brain , 1996, Neurology.

[30]  D. Firth Bias reduction of maximum likelihood estimates , 1993 .

[31]  M. Pessin,et al.  Neuroradiologic evaluation of patients with acute stroke treated with recombinant tissue plasminogen activator. The rt-PA Acute Stroke Study Group. , 1993, AJNR. American journal of neuroradiology.

[32]  R. Hart,et al.  Early recurrent embolism associated with nonvalvular atrial fibrillation: a retrospective study. , 1983, Stroke.

[33]  N. Mantel Evaluation of survival data and two new rank order statistics arising in its consideration. , 1966, Cancer chemotherapy reports.

[34]  Silvia G. Priori,et al.  ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association task force on practice guidelines and the European society of cardiology committee for PRAC , 2006 .