Anticoagulation in patients with auricular fibrilation and amiloid angiopathy Review of a complex subject based on scientific literature
Keywords:
cerebral amyloid angiopathy, atrial fibrillation, anticoagulation, intracerebral hemorrhage, thrombosisAbstract
The risk of ischemic stroke in atrial fibrillation can be quantified by the CHA2DS2-VASc score. High risk patients according to the CHA2DS2-VASC score should be anticoagulated, however cerebral amyloid angiopathy increases the risk of intracranial hemorrhage. This review aims to highlight the current management of patients with cerebral amyloid angiopathy and atrial fibrillation. Bleeding biomarkers for cerebral amyloid angiopathy include cortical microhemorrhages, cortical superficial siderosis, convex subarachnoid hemorrhage, deep intracerebral hemorrhage, and lobar hemorrhage. The scientific evidence indicates that deep intracerebral hemorrhage has an annual recurrence rate of 8,9% and for annual lobar hemorrhage it is greater than 19%. Cortical microhemorrhages increase the risk of deep and lobar intracerebral hemorrhage with the prescription of oral anticoagulants, with a dose-dependent effect. In patients with atrial fibrillation, anticoagulants should be avoided in the presence of cerebral amyloid angiopathy and predominant bleeding risk characteristics such as superficial cortical siderosis or deep intracerebral hemorrhage. A randomized controlled trial comparing oral anticoagulants with a left atrial appendage closure device would help resolve this thrombosis-bleeding dilemma in these patients.
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References
Poels MM, Vernooiji MW, Ikram MA, Hofman A, Krestin GP, van der Lugt A, et al. Prevalence and risk factors of cerebral microbleeds: an update of the Rotterdam scan study. Stroke 2010; 41(10 Suppl): S103–6.
Charidimou A, Karayiannis C, Song TJ, Orken DN, Thijs V, Lemmens R, et al. Brain microbleeds, anticoagulation, and hemorrhage risk: meta-analysis in stroke patients with AF. Neurology 2017; 89(23): 2317–26.
Keage HA, Carare RO, Friedland RP, Ince PG, Love S, Nicoll JA, et al. Population studies of sporadic cerebral amyloid angiopathy and dementia: a systematic review. BMC Neurol 2009; 9:3.
Charidimou A, Boulouis G, Gurol ME, Ayata C, Bacskai BJ, Frosch MP, et al. Emerging concepts in sporadic cerebral amyloid angiopathy. Brain 2017; 140(7): 1829–50.
Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010; 9(7): 689–701.
Keable A, Fenna K, Yuen HM, Johnston DA, Smyth NR, Smith C, et al. Deposition of amyloid beta in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy. Biochim Biophys Acta 2016; 1862(5): 1037–46.
Weller RO, Subash M, Preston SD, Mazanti I, Carare RO. Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer's disease. Brain Pathol 2008; 18(2): 253–66.
Greenberg SM, Charidimou A. Diagnosis of cerebral amyloid angiopathy: evolution of the Boston criteria. Stroke 2018; 49(2): 491–7.
Charidimou A, Meegahage R, Fox Z, Peeters A, Vandermeeren Y, Laloux P, et al. Enlarged perivascular spaces as a marker of underlying arteriopathy in intracerebral haemorrhage: a multicentre MRI cohort study. J Neurol Neurosurg Psychiatry 2013; 84(6): 624–9.
January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, et al. 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. J Am Coll Cardiol 2014; 64(21): e1–76.
DeSimone CV, Graff-Radford J, El-Harasis MA, Rabinstein AA, Asirvatham SJ, Holmes DR Jr. Cerebral amyloid Angiopathy. J Am Coll Cardiol 2017; 70(9): 1173–82.
Siontis KC, Geske JB, Gersh BJ. Atrial fibrillation pathophysiology and prognosis: insights from cardiovascular imaging. Circ Cardiovasc Imaging 2015; 8(6).
Frenkel D, D’Amato SA, Al-Kazaz M, Markowitz SM, Liu CF, Thomas G, et al. Prevalence of left atrial Thrombus detection by transesophageal echocardiography: a comparison of continuous non-vitamin K antagonist oral anticoagulant versus warfarin therapy in patients undergoing catheter ablation for atrial fibrillation. JACC Clin Electrophysiol 2016; 2(3): 295–303.
Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001; 285(22): 2864-70.
Yaghi S, Kamel H. Stratifying stroke risk in atrial fibrillation: beyond clinical risk scores. Stroke 2017; 48(10): 2665–70.
Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. 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. Chest 2010; 137(2): 263–72.
Pisters R, Lane DA, NieuwOAIt R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the euro heart survey. Chest 2010; 138(5): 1093–100.
Mitchell LB, Southern DA, Galbraith D, Ghali WA, Knudtson M, Wilton SB, et al. Prediction of stroke or TIA in patients without atrial fibrillation using CHADS2 and CHA2DS2-VASc scores. Heart 2014; 100(19): 1524–30.
Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369(22): 2093–104.
Swiryn S, Orlov MV, Benditt DG, DiMarco JP, Lloyd-Jones DM, Karst E, et al. Clinical implications of brief device-detected atrial tachyarrhythmias in a cardiac rhythm management device population: results from the registry of atrial tachycardia and atrial fibrillation episodes. Circulation 2016; 134(16): 1130–40.
Boriani G, Glotzer TV, Santini M, West TM, De Melis M, Sepsi M, et al. Device-detected atrial fibrillation and risk for stroke: an analysis of > 10,000 patients from the SOS AF project (stroke prevention strategies based on atrial fibrillation information from implanted devices). Eur Heart J 2014; 35(8): 508–16.
Goldman ME, Pearce LA, Hart RG, Zabalgoitia M, Asinger RW, Safford R, et al. Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation: I. Reduced flow velocity in the left atrial appendage (the stroke prevention in atrial fibrillation [SPAFIII] study). J Am Soc Echocardiogr 1999; 12(12): 1080–7.
Korhonen M, Parkkonen J, Hedman M, Muuronen A, Onatsu J, Mustonen P, et al. Morphological features of the left atrial appendage in consecutive coronary computed tomography angiography patients with and without atrial fibrillation. PLoS One 2017; 12(3): e0173703.
Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146(12): 857–67.
Stroke Prevention in Atrial Fibrillation Study. Final results. Circulation 1991; 84(2): 527–39.
Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study. Lancet 1994; 343(8899): 687–91.
ACTIVE Writing Group of the ACTIVE Investigators, Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial Fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006; 367(9526): 1903–12.
Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361(12): 1139–51.
Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S, et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011; 364(9): 806–17.
O’Donnell MJ, Eikelboom JW, Yusuf S, Diener HC, Hart RG, Smith EE, et al. Effect of apixaban on brain infarction and microbleeds: AVERROES-MRI assessment study. Am Heart J 2016; 178:145–50.
Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365(11): 981–92.
Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol 2013; 12(5): 483–97.
Wilson D, Charidimou A, Ambler G, Fox ZV, Gregoire S, Rayson P, et al. Recurrent stroke risk and cerebral microbleed burden in ischemic stroke and TIA: a meta-analysis. Neurology 2016; 87(14): 1501–10.
Charidimou A, Boulouis G, Xiong L, Jessel MJ, Roongpiboonsopit D, Ayres A, et al. Cortical superficial siderosis and first-ever cerebral hemorrhage in cerebral amyloid angiopathy. Neurology 2017; 88(17): 1607–14.
Wilson D, Hostettler IC, Ambler G, Banerjee G, Jager HR, Werring DJ. Convexity subarachnoid haemorrhage has a high risk of intracerebral haemorrhage in suspected cerebral amyloid angiopathy. J Neurol 2017; 264(4): 664–73.
Charidimou A, Linn J, Vernooij MW, Opherk C, Akoudad S, Baron JC, et al. Cortical superficial siderosis: detection and clinical significance in cerebral amyloid angiopathy and related conditions. Brain 2015; 138(Pt 8): 2126–39.
van Etten ES, Gurol ME, van der Grond J, Haan J, Viswanathan A, Schwab KM, et al. Recurrent hemorrhage risk and mortality in hereditary and sporadic cerebral amyloid angiopathy. Neurology 2016; 87(14):1482–7.
Rosand J, Eckman MH, Knudsen KA, Singer DE, Greenberg SM. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med 2004; 164(8):880–4.
Banerjee G, Carare R, Cordonnier C, Greenberg SM, Schneider JA, Smith EE, et al. The increasing impact of cerebral amyloid angiopathy: essential new insights for clinical practice. J Neurol Neurosurg Psychiatry 2017; 88(11): 982–94.
Wilson D, Ambler G, Shakeshaft C, Brown MM, Charidimou A, Al-Shahi Salman R, et al. Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study. Lancet Neurol 2018; 17(6): 539–47.
Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H, Buchbinder M, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet 2009; 374(9689): 534–42.
Holmes DR Jr, Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK, et al. Prospective randomized evaluation of the WATCHMAN Left Atrial Appendage Closure Device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol 2014; 64(1): 1–12.
Reddy VY, Mobius-Winkler S, Miller MA, Neuzil P, Schuler G, Wiebe J, et al. Left atrial appendage closure with the Watchman device in patients with a contraindication for oral anticoagulation: the ASAP study (ASA Plavix feasibility study with WATCHMAN Left Atrial Appendage Closure Technology). J Am Coll Cardiol 2013; 61(25): 2551–6.
Dukkipati SR, Kar S, Holmes DR, Jr., Doshi SK, Swarup V, Gibson DN, et al. Device-related thrombus after left atrial appendage closure: incidence, predictors, and outcomes. Circulation 2018; 138(9): 874-885.
Banerjee G, Wilson D, Ambler G, Osei-Bonsu Appiah K, Shakeshaft C, Lunawat S, et al. Cognitive impairment before intracerebral hemorrhage is associated with cerebral amyloid angiopathy. Stroke 2018; 49(1): 40–5.
Charidimou A, Farid K, Baron JC. Amyloid-PET in sporadic cerebral amyloid angiopathy: a diagnostic accuracy meta-analysis. Neurology 2017; 89(14): 1490–8.
Gurol ME, Becker JA, Fotiadis P, Riley G, Schwab K, Johnson KA, et al. Florbetapir-PET to diagnose cerebral amyloid angiopathy: a prospective study. Neurology 2016; 87(19): 2043–9.
Wermer MJH, Greenberg SM. The growing clinical spectrum of cerebral amyloid angiopathy. Curr Opin Neurol 2018; 31(1): 28–35.
Kam W, Holmes DN, Hernandez AF, Saver JL, Fonarow GC, Smith EE, et al. Association of Recent Use of Non-Vitamin K Antagonist Oral Anticoagulants With Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase. JAMA 2022; 327(8): 760-771.
Choi KH, Kim JH, Lee C, Kim JM, Kang KW, Kim JT, et al. Microbleeds and Outcome in Patients With Acute Ischemic Stroke and Atrial Fibrillation Taking Anticoagulants. Stroke 2020; 51(12): 3514-3522.
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