Safety of Apixaban Monotherapy for Non-Valvular Atrial Fibrillation-Related Acute Stroke with Intra-/Extracranial Artery Stenosis

Introduction: We investigated whether apixaban is safe for the prevention of further adverse events in non-valvular atrial fibrillation (NVAF) patients with intra-/extracranial artery stenosis (Stenosis group) compared with acute large vessel occlusion without intra-/extracranial artery stenosis (No stenosis group). We also examined whether combination therapy using apixaban and antiplatelet is safe. Methods: ALVO (Apixaban on clinical outcome of patients with Large Vessel Occlusion [LVO] or stenosis) was a historical and prospective multicenter registry at 38 centers in Japan. Patients with NVAF and acute LVO or stenosis who received apixaban within 14 days after onset were included. We conducted the post hoc analysis using the ALVO dataset. We compared patients with stenosis versus those without stenosis in terms of the primary outcome, which was defined as a composite of all-cause death, major bleeding events, and ischemic events 365 days after onset. Results: Of the 662 patients, 54 (8.2%) patients were classified into the Stenosis group, and 104 patients of the total (16%) reached the primary outcome. The cumulative incidence of primary outcome was not significantly different between the No stenosis and the Stenosis groups (hazard ratio [HR] 1.2, 95% confidence interval [CI]: 0.64–2.4; p = 0.52). Even after adjustment for predictive clinical variates, no significant difference in the primary endpoint between the No stenosis and the Stenosis groups was shown (adjusted HR 1.2, 95% CI: 0.59–2.5; p = 0.60). Fifty patients (7.6%) used an antiplatelet with apixaban. Among the Stenosis group patients, the cumulative incidence of the primary outcome was significantly higher among patients treated with an antiplatelet and apixaban (HR 3.5, 95% CI: 1.0–12; p = 0.048). Conclusion: Apixaban monotherapy appears safe for the prevention of further adverse events in the Stenosis group patients similar to the No stenosis group patients. Concomitant use of an antiplatelet might not be favorable in patients with stenosis.

[1]  M. Ezura,et al.  Safety of Early Administration of Apixaban on Clinical Outcomes in Patients with Acute Large Vessel Occlusion , 2020, Translational Stroke Research.

[2]  P. Gorelick,et al.  Effectiveness of Adding Antiplatelets to Oral Anticoagulants in Patients with Acute Ischemic Stroke with Atrial Fibrillation and Concomitant Large Artery Steno-Occlusion , 2020, Translational Stroke Research.

[3]  M. Khan,et al.  Dual Versus Triple Therapy for Atrial Fibrillation After Percutaneous Coronary Intervention , 2020, Annals of Internal Medicine.

[4]  N. Hagiwara,et al.  Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease. , 2019, The New England journal of medicine.

[5]  K. Ogasawara,et al.  Endovascular Therapy in Ischemic Stroke With Acute Large‐Vessel Occlusion: Recovery by Endovascular Salvage for Cerebral Ultra‐Acute Embolism Japan Registry 2 , 2018, Journal of the American Heart Association.

[6]  G. Lip,et al.  Antithrombotic management in patients with atrial fibrillation undergoing coronary stent implantation: What is the impact of guideline adherence? , 2016, International journal of cardiology.

[7]  D. Atar,et al.  Mass screening for silent atrial fibrillation in high risk patients - preliminary results from the STROKESTOP trial , 2013 .

[8]  E. Mori,et al.  Guidelines for the intravenous application of recombinant tissue-type plasminogen activator (alteplase), the second edition, October 2012: a guideline from the Japan Stroke Society. , 2013, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[9]  M. Hennerici,et al.  Comparison of the European and Japanese Guidelines for the Acute Management of Intracerebral Hemorrhage , 2013, Cerebrovascular Diseases.

[10]  G. Breithardt,et al.  Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF , 2012, The Lancet Neurology.

[11]  P. Loewen,et al.  Risk of bleeding with oral anticoagulants: an updated systematic review and performance analysis of clinical prediction rules , 2011, Annals of Hematology.

[12]  Jinkwon Kim,et al.  Increases in Cerebral Atherosclerosis According to CHADS2 Scores in Patients With Stroke With Nonvalvular Atrial Fibrillation , 2011, Stroke.

[13]  Jun Zhu,et al.  Apixaban in patients with atrial fibrillation. , 2011, The New England journal of medicine.

[14]  Gregory Y H Lip,et al.  Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. , 2011, Journal of the American College of Cardiology.

[15]  Fredrik Folke,et al.  Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. , 2010, Archives of internal medicine.

[16]  P. Barber,et al.  Pathophysiological Determinants of Worse Stroke Outcome in Atrial Fibrillation , 2010, Cerebrovascular Diseases.

[17]  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.

[18]  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.

[19]  M. Monreal,et al.  Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry , 2008, Thrombosis and Haemostasis.

[20]  B. Ince,et al.  Atherothrombotic ischemic stroke in patients with atrial fibrillation , 2007, Clinical Neurology and Neurosurgery.

[21]  M. Aguilar,et al.  Meta-analysis: Antithrombotic Therapy to Prevent Stroke in Patients Who Have Nonvalvular Atrial Fibrillation , 2007, Annals of Internal Medicine.

[22]  S. Sacco,et al.  Contribution of Atrial Fibrillation to Incidence and Outcome of Ischemic Stroke: Results From a Population-Based Study , 2005, Stroke.

[23]  K. Minematsu,et al.  Atrial fibrillation as a predictive factor for severe stroke and early death in 15 831 patients with acute ischaemic stroke , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[24]  A. Waldo.  Stroke prevention in atrial fibrillation. , 2003, JAMA.

[25]  M. Rich,et al.  Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. , 2001, JAMA.

[26]  D. Singer,et al.  Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. , 2001, JAMA.

[27]  T. Brott,et al.  Improved Reliability of the NIH Stroke Scale Using Video Training , 1994, Stroke.

[28]  P. Wolf,et al.  Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. , 1991, Stroke.

[29]  A. Belanger,et al.  The Framingham study. , 1976, British medical journal.

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

[31]  R. Bloch,et al.  Interobserver agreement for the assessment of handicap in stroke patients. , 1988, Stroke.