randomized studies in other populations are needed before we can recommend the widespread use of early rhythm control in patients with stroke and AF. https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 12/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Control of hypertension Blood pressure control is an important component of the management of patients with AF who have had a stroke. Antihypertensive therapy, preferably including an angiotensin-converting enzyme inhibitor, reduces the risk of vitamin K antagonist (VKA)-associated intracranial hemorrhage and may reduce the rate of recurrent stroke. (See "Reversal of anticoagulation in intracranial hemorrhage".) The latter benefit was suggested in a secondary analysis from the PROGRESS trial, which demonstrated the benefit of blood pressure lowering (using perindopril-indapamide) among both hypertensive and nonhypertensive patients who had a previous stroke or transient ischemic attack (TIA) [49]. (See "Antihypertensive therapy for secondary stroke prevention".) Among the subset of 476 patients with AF, perindopril-based therapy produced a mean 7.3/3.4 mmHg reduction in blood pressure compared with placebo and a 34 percent reduction in the incidence of recurrent stroke (13.6 versus 18.9 percent), a difference that was not statistically significant because of the small number of recurrent events [50]. However, there was a significant 38 percent reduction in all major vascular events (one major vascular event prevented in every 11 patients treated for five years), providing a strong rationale for blood pressure lowering. Revascularization for carotid artery stenosis About 10 percent of patients with AF with ischemic stroke or TIA have a cervical carotid stenosis of 50 percent or greater diameter, slightly more than half of which are ipsilateral to the neurological symptoms. Based on estimates of attributable risk, ipsilateral stenosis of at least 70 percent stenosis is equally likely to be the cause of cerebral ischemia as is cardiogenic embolism. Consequently, carotid revascularization with endarterectomy or stenting seems reasonable for AF patients with high-grade ipsilateral stenosis, followed by chronic anticoagulation and antiplatelet therapy, although this approach is empiric, without good supporting evidence, and the use of combined antiplatelet and anticoagulant therapy increases bleeding risk. The management of symptomatic carotid artery disease is discussed elsewhere. (See "Management of symptomatic carotid atherosclerotic disease".) Statin therapy For most patients with ischemic stroke, we start statin therapy. Statin therapy reduces the risk of recurrent ischemic stroke and cardiovascular events among patients with stroke of atherosclerotic origin, although the efficacy of statin therapy specifically for patients with ischemic stroke attributed to AF has not been well studied. However, a report of 6116 patients with ischemic stroke who were discharged on a statin found that outpatient adherence to statin therapy was associated with a reduced risk of recurrent ischemic stroke for patients with AF as well as those without AF, even after https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 13/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate adjustment for time in the therapeutic range of the international normalized ratio (INR) among patients with AF taking warfarin [51]. Many patients with AF have concomitant atherosclerotic disease, and statin therapy is recommended for patients with atherosclerotic cardiovascular disease (such as prior acute coronary syndrome, myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, ischemic stroke, TIA, or peripheral arterial disease) (see "Overview of secondary prevention of ischemic stroke", section on 'LDL-C lowering therapy'). In addition, and in the absence of defined atherosclerotic cardiovascular disease, many patients are at high risk for a cardiovascular disease event due to age and the presence of hypertension. (See "Low- density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease", section on 'Age >75 years'.) Lifestyle modification A number of behavioral and lifestyle modifications may be beneficial for reducing the risk of ischemic stroke and cardiovascular disease. These include smoking cessation, limited alcohol consumption, weight control, regular aerobic physical activity, salt restriction, and a Mediterranean diet. (See "Overview of secondary prevention of ischemic stroke", section on 'Lifestyle modification'.) SUMMARY AND RECOMMENDATIONS Features suggestive of cardioembolic stroke Cardioembolic stroke from atrial fibrillation (AF) is generally associated with increased severity compared with embolic stroke from carotid disease. Cardioembolic stroke may affect single or multiple vascular territories of the brain and appear as wedge-shaped infarcts involving cortex and adjacent white matter. (See 'Features suggestive of cardioembolic stroke' above.) Evaluation for reperfusion therapy All patients with acute ischemic stroke should be assessed to see if they are eligible for reperfusion therapy. (See 'Is reperfusion therapy indicated?' above.) Comprehensive stroke evaluation All patients with acute stroke, even in the setting of AF, need a complete evaluation for other causes of stroke; the work-up should include brain and neurovascular imaging, cardiac rhythm monitoring, and echocardiography. Paroxysmal AF may not be detected on short-term cardiac monitoring; thus, ambulatory cardiac monitoring for several weeks is suggested for all adult patients with a cryptogenic ischemic stroke or cryptogenic transient ischemic attack (TIA). (See 'Diagnostic approach' above.) https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 14/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Antithrombotic therapy during the acute phase of stroke Anticoagulation is usually temporarily withheld immediately after ischemic stroke, due to the risk of hemorrhagic transformation, and restarted within the first days to two weeks, as guided mainly by the size of the ischemic infarct. (See 'Timing after acute ischemic stroke' above.) For patients with AF and large acute infarctions, symptomatic hemorrhagic transformation, or poorly controlled hypertension, we suggest withholding oral anticoagulation for one to two weeks (Grade 2C). (See 'Timing after acute ischemic stroke' above.) However, early acute antiplatelet therapy ( algorithm 2) may be warranted to reduce both disability and the risk of early recurrent stroke, which is 3 to 5 percent in the first two weeks. (See 'Managing antithrombotic therapy acutely' above.) Long-term anticoagulation For most patients with an ischemic stroke or TIA and AF, we recommend a direct-acting oral anticoagulant (DOAC) rather than a vitamin K antagonist (VKA) (Grade 1A). DOACs are more efficacious at preventing recurrent stroke and have lower rates of major hemorrhage. However, a VKA is indicated for patients with moderate to severe mitral stenosis or any mechanical heart valve and is generally preferred for patients with severely impaired kidney function. (See 'Long-term anticoagulation' above.) Anticoagulation treatment failure Determining the cause For patients with AF who develop an ischemic stroke while on anticoagulation, subtherapeutic intensity of anticoagulation (eg, inappropriate low-dose DOAC, missed DOAC doses, or low international normalized ratio [INR] on warfarin) at the time of stroke is the most common cause of treatment failure. Nevertheless, all such patients should have a thorough evaluation (including brain and neurovascular imaging, and echocardiography) to determine if the most likely cause of stroke is cardioembolic due to AF, or noncardioembolic due to another mechanism. (See 'Determining the cause of recurrent stroke' above.) DOAC treatment failure In this setting, it is important to verify that the correct DOAC dose is prescribed and that the patient is compliant. If a thrombus is present despite appropriate dosing and compliance, it is reasonable to change to another DOAC, but optimal treatment is uncertain. (See 'Direct-acting oral anticoagulant treatment failure' above.) Warfarin treatment failure In this setting, options include increasing the target INR to 2.5 to 3.5, switching to a DOAC, or considering LAA occlusion. For patients with a subtherapeutic INR at the time of the stroke, an attempt should be made to identify the https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 15/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate cause (eg, poor compliance, drug or food interaction) and to consider switching to a DOAC if the annual time in therapeutic range has been less than 70 percent. Hemorrhagic stroke on anticoagulation For patients on anticoagulation who develop a hemorrhagic stroke, anticoagulation and antiplatelet drugs should be discontinued, and medications to reverse the effects of anticoagulant drugs should be given immediately. These and other measures are reviewed separately. (See "Reversal of anticoagulation in intracranial hemorrhage" and "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis".) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Anderson DC, Kappelle LJ, Eliasziw M, et al. Occurrence of hemispheric and retinal ischemia in atrial fibrillation compared with carotid stenosis. Stroke 2002; 33:1963. 2. Harrison MJ, Marshall J. Atrial fibrillation, TIAs and completed strokes. Stroke 1984; 15:441. 3. Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial fibrillation. The Framingham Study. Stroke 1996; 27:1760. 4. J rgensen HS, Nakayama H, Reith J, et al. Acute stroke with atrial fibrillation. 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Timing of Initiation of Oral Anticoagulation after Acute Ischemic Stroke in Patients with Atrial Fibrillation. Pharmacotherapy 2020; 40:55. 36. Lansberg MG, O'Donnell MJ, Khatri P, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e601S. https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 18/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate 37. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45:2160. 38. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37:2893. 39. Chen ZM, Sandercock P, Pan HC, et al. Indications for early aspirin use in acute ischemic stroke : A combined analysis of 40 000 randomized patients from the chinese acute stroke trial and the international stroke trial. On behalf of the CAST and IST collaborative groups. Stroke 2000; 31:1240. 40. Evans A, Perez I, Yu G, Kalra L. Should stroke subtype influence anticoagulation decisions to prevent recurrence in stroke patients with atrial fibrillation? Stroke 2001; 32:2828. 41. Connolly BJ, Pearce LA, Hart RG. Vitamin K antagonists and risk of subdural hematoma: meta-analysis of randomized clinical trials. Stroke 2014; 45:1672. 42. Gladstone DJ, Bui E, Fang J, et al. Potentially preventable strokes in high-risk patients with atrial fibrillation who are not adequately anticoagulated. Stroke 2009; 40:235. 43. Yaghi S, Liberman AL, Henninger N, et al. 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Topic 1059 Version 46.0 https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 20/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate GRAPHICS Eligibility criteria for the treatment of acute ischemic stroke with intravenous thrombolysis (recombinant tissue plasminogen activator or tPA) Inclusion criteria Clinical diagnosis of ischemic stroke causing measurable neurologic deficit Onset of symptoms <4.5 hours before beginning treatment; if the exact time of stroke onset is not known, it is defined as the last time the patient was known to be normal or at neurologic baseline Age 18 years Exclusion criteria Patient history Ischemic stroke or severe head trauma in the previous three months Previous intracranial hemorrhage Intra-axial intracranial neoplasm Gastrointestinal malignancy Gastrointestinal hemorrhage in the previous 21 days Intracranial or intraspinal surgery within the prior three months Clinical Symptoms suggestive of subarachnoid hemorrhage Persistent blood pressure elevation (systolic 185 mmHg or diastolic 110 mmHg) Active internal bleeding Presentation consistent with infective endocarditis Stroke known or suspected to be associated with aortic arch dissection Acute bleeding diathesis, including but not limited to conditions defined under 'Hematologic' Hematologic 3 Platelet count <100,000/mm * Current anticoagulant use with an INR >1.7 or PT >15 seconds or aPTT >40 seconds* Therapeutic doses of low molecular weight heparin received within 24 hours (eg, to treat VTE and ACS); this exclusion does not apply to prophylactic doses (eg, to prevent VTE) Current use (ie, last dose within 48 hours in a patient with normal renal function) of a direct thrombin inhibitor or direct factor Xa inhibitor with evidence of anticoagulant effect by laboratory tests such as aPTT, INR, ECT, TT, or appropriate factor Xa activity assays Head CT https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 21/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Evidence of hemorrhage Extensive regions of obvious hypodensity consistent with irreversible injury Warnings Only minor and isolated neurologic signs or rapidly improving symptoms Serum glucose <50 mg/dL (<2.8 mmol/L) Serious trauma in the previous 14 days Major surgery in the previous 14 days History of gastrointestinal bleeding (remote) or genitourinary bleeding Seizure at the onset of stroke with postictal neurologic impairments Pregnancy** Arterial puncture at a noncompressible site in the previous seven days Large ( 10 mm), untreated, unruptured intracranial aneurysm Untreated intracranial vascular malformation Additional warnings for treatment from 3 to 4.5 hours from symptom onset Age >80 years Oral anticoagulant use regardless of INR Severe stroke (NIHSS score >25) Combination of both previous ischemic stroke and diabetes mellitus ACS: acute coronary syndrome; aPTT: activated partial thromboplastin time; ECT: ecarin clotting time; INR: international normalized ratio; PT: prothrombin time; NIHSS: National Institutes of Health Stroke Scale; tPA: intravenous alteplase; TT: thrombin time; VTE: venous thromboembolism. Although it is desirable to know the results of these tests, thrombolytic therapy should not be delayed while results are pending unless (1) there is clinical suspicion of a bleeding abnormality or thrombocytopenia, (2) the patient is currently on or has recently received anticoagulants (eg, heparin, warfarin, a direct thrombin inhibitor, or a direct factor Xa inhibitor), or (3) use of anticoagulants is not known. Otherwise, treatment with intravenous tPA can be started before availability of coagulation test results but should be discontinued if the INR, PT, or aPTT exceed the limits stated in the table, or 3 if platelet count is <100,000 mm . With careful consideration and weighting of risk-to-benefit, patients may receive intravenous alteplase despite one or more warnings. Patients who have a persistent neurologic deficit that is potentially disabling, despite improvement of any degree, should be treated with tPA in the absence of other contraindications. Any of the following should be considered disabling deficits: Complete hemianopia: 2 on NIHSS question 3, or Severe aphasia: 2 on NIHSS question 9, or Visual or sensory extinction: 1 on NIHSS question 11, or https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 22/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Any weakness limiting sustained effort against gravity: 2 on NIHSS question 5 or 6, or Any deficits that lead to a total NIHSS >5, or Any remaining deficit considered potentially disabling in the view of the patient and the treating practitioner using clinical judgment Patients may be treated with intravenous alteplase if glucose level is subsequently normalized. The potential risks of bleeding with alteplase from injuries related to the trauma should be weighed against the anticipated benefits of reduced stroke-related neurologic deficits. The increased risk of surgical site bleeding with alteplase should be weighed against the anticipated benefits of reduced stroke-related neurologic deficits. There is a low increased risk of new bleeding with alteplase in the setting of past gastrointestinal or genitourinary bleeding. However, alteplase administration within 21 days of gastrointestinal bleeding is not recommended. Alteplase is reasonable in patients with a seizure at stroke onset if evidence suggests that residual impairments are secondary to acute ischemic stroke and not to a postictal phenomenon. * Alteplase can be given in pregnancy when the anticipated benefits of treating moderate or severe stroke outweigh the anticipated increased risks of uterine bleeding. The safety and efficacy of administering alteplase is uncertain for these relative exclusions. Although these were exclusions in the trial showing benefit in the 3 to 4.5 hour window, intravenous alteplase appears to be safe and may be beneficial for patients with these criteria, including patients taking oral anticoagulants with an INR <1.7. Adapted from: 1. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; 359:1317. 2. Del Zoppo GJ, Saver JL, Jauch EC, et al. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator. A science advisory from the American Heart Association/American Stroke Association. Stroke 2009; 40:2945. 3. Re-examining Acute Eligibility for Thrombolysis (TREAT) Task Force:, Levine SR, Khatri P, et al. Review, historical context, and clari cations of the NINDS rt-PA stroke trials exclusion criteria: Part 1: rapidly improving stroke symptoms. Stroke 2013; 44:2500. 4. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scienti c rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2016; 47:581. 5. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2019; 50:e344. Graphic 71462 Version 26.0 https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 23/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Indications for mechanical thrombectomy to treat patients with acute ischemic IV: intravenous; tPA: tissue plasminogen activator (alteplase or tenecteplase); CTA: computed tomography an artery occlusion; MT: mechanical thrombectomy; ASPECTS: Alberta Stroke Program Early CT Score; NIHSS: Na tomography; MRI: magnetic resonance imaging; mRS: modified Rankin Scale; MCA: middle cerebral artery; IC recovery. Patients are not ordinarily eligible for IV tPA unless the time last known to be well is <4.5 hours. However, im that is diffusion positive and FLAIR negative) is an option at expert stroke centers to select patients with wake associated UpToDate topics for details. Usually assessed with MRA or CTA, less often with digital subtraction angiography. There is intracranial arterial occlusion of the distal ICA, middle cerebral (M1/M2), or anterior cerebral (A1/A2 MT may be a treatment option for patients with acute ischemic stroke caused by occlusion of the basilar ar stroke centers, but benefit is uncertain. [1] Based upon data from the Aurora study . Reference: https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 24/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate 1. Albers GW, Lansberg MG, Brown S, et al. Assessment of Optimal Patient Selection for Endovascular Thrombectomy Beyond 6 Hou Neurol 2021; 78:1064. Graphic 117086 Version 3.0 https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 25/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Pathophysiologic ischemic stroke classification Large vessel atherothrombotic stroke More common Bifurcation of the common carotid artery Siphon portion of the common carotid artery Middle cerebral artery stem Intracranial vertebral arteries proximal to middle basilar artery Origin of the vertebral arteries Less common Origin of the common carotid artery Posterior cerebral artery stem Origin of the major branches of the basilar-vertebral arteries Origin of the branches of the anterior, middle, and posterior cerebral arteries Small vessel (lacunar) stroke Mechanism Lipohyalinotic occlusion Less frequently proximal atherothrombotic occlusion Least likely embolic occlusion Most common locations Penetrating branches of the anterior, middle, and posterior cerebral and basilar arteries Cardioaortic embolic stroke Cardiac sources definite - antithrombotic therapy generally used Left atrial thrombus Left ventricular thrombus Atrial fibrillation and paroxysmal atrial fibrillation Sustained atrial flutter Recent myocardial infarction (within one month) Rheumatic mitral or aortic valve disease Bioprosthetic and mechanical heart valve Chronic myocardial infarction with ejection fraction <28 percent https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 26/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Symptomatic heart failure with ejection fraction <30 percent Dilated cardiomyopathy Cardiac sources definite - anticoagulation hazardous Bacterial endocarditis (exception nonbacterial) Atrial myxoma Cardiac sources possible Mitral annular calcification Patent foramen ovale Atrial septal aneurysm Atrial septal aneurysm with patent foramen ovale Left ventricular aneurysm without thrombus Isolated left atrial spontaneous echo contrast ("smoke") without mitral stenosis or atrial fibrillation Mitral valve strands Ascending aortic atheromatous disease (>4 mm) True unknown source embolic stroke Other Dissection Moyamoya Binswanger's disease Primary thrombosis Cerebral mass Graphic 55099 Version 4.0 https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 27/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Immediate antithrombotic treatment of acute ischemic stroke This algorithm is intended to provide basic guidance regarding the immediated use of antithrombotic therapy for patients with an acute ischemic stroke. For further details, including scoring of the NIHSS and suggested dosing regimens of antithrombotic agents, refer to the relevant UpToDate topic reviews. OA: oral anticoagulants; IVT: intravenous thrombolysis; MT: mechanical thrombectomy; NIHSS: National Institutes of Health Stroke Scale; DAPT: dual antiplatelet therapy (eg, aspirin and clopidogrel, or aspirin and ticagrelor). Refer to text and associated algorithm for details. Brain and large vessel imaging, cardiac evaluation, and (for select patients) other laboratory tests. https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 28/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate For severe systemic or symptomatic intracranial bleeding, withhold all anticoagulant and antiplatelet therapy for one to two weeks or until the patient is stable. Graphic 131697 Version 2.0 https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 29/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Antithrombotic therapy according to cause of acute ischemic stroke This algorithm is intended to provide basic guidance regarding the immediate use of antithrombotic therapy with an acute ischemic stroke. For further details, including scoring of the NIHSS and suggested dosing regim antithrombotic agents, refer to the relevant UpToDate topic reviews. https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 30/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate HTN: hypertension; SBP: systolic blood pressure; DBP: diastolic blood pressure; ICA: internal carotid artery; C endarterectomy; OA: oral anticoagulation; CAS: carotid artery stenting; DAPT: dual antiplatelet therapy (eg, a clopidogrel, or aspirin and ticagrelor); NIHSS: National Institutes of Health Stroke Scale; CT: computed tomog magnetic resonance imaging. Brain and neurovascular imaging, cardiac evaluation, and (for select patients) other laboratory tests. Indications for long-term oral anticoagulation include atrial fibrillation, ventricular thrombus, mechanical h treatment of venous thromboembolism. "Large" infarcts are defined as those that involve more than one-third of the middle cerebral artery territor one-half of the posterior cerebral artery territory based upon neuroimaging with CT or MRI. Though less relia infarct size can also be defined clinically (eg, NIHSS score >15). Long-term aspirin therapy is alternative (though less effective) if OA contraindicated or refused. Direct oral anticoagulant agents have a more rapid anticoagulant effect than warfarin, a factor that may inf choice of agent and timing of OA initiation. Some experts prefer DAPT, based upon observational evidence. Long-term single-agent antiplatelet therapy for secondary stroke prevention with aspirin, clopidogrel, or as release dipyridamole. Graphic 131701 Version 2.0 https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 31/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Standard dosing of direct oral anticoagulants Nonvalvular AF - VTE primary Anticoagulant stroke VTE treatment prophylaxis prophylaxis* Dabigatran (Pradaxa) 150 mg twice daily Parenteral 110 mg for the first anticoagulation for 5 to day, then 220 mg once 10 days; then dabigatran 150 mg twice daily daily Apixaban (Eliquis) 5 mg twice daily 10 mg twice daily for one week, then 5 mg 2.5 mg twice daily twice daily Edoxaban (Savaysa, Lixiana) 60 mg once daily Parenteral anticoagulation for 5 to 10 days; then edoxaban 60 mg once daily Rivaroxaban (Xarelto) 20 mg once daily with the evening meal 15 mg twice daily with food for three weeks; then 20 mg once daily with food 10 mg once daily, with or without food This is a simplified table that lists the most common dosing in individuals with normal renal function, normal weight, and lack of concomitant interacting medications (eg, P-glycoprotein inhibitors or inducers). Refer to UpToDate topics on AF, VTE treatment, VTE prophylaxis, and DOAC dosing for possible changes based on impaired renal function or extremes of weight. Other factors may influence dosing in individual patients. AF: atrial fibrillation; VTE: venous thromboembolism, includes deep vein thrombosis and pulmonary embolism; DOAC: direct oral anticoagulant. Dosing may be reduced for certain drugs in certain settings (eg, use of dabigatran 110 mg twice daily for individuals who are at increased risk of bleeding; refer to UpToDate topic on anticoagulation for atrial fibrillation for other examples). Treatment for acute VTE typically refers to the first three to six months of administration; continued treatment beyond six months may be done with a lower dose for some anticoagulants (eg, apixaban, rivaroxaban); the dose is not lowered when therapy is continued using dabigatran or edoxaban. Refer to the latest prescribing information for each individual anticoagulant. Prophylaxis refers to primary prophylaxis in settings such as after knee or hip surgery. https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 32/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Graphic 112514 Version 5.0 https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 33/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Contributor Disclosures Warren J Manning, MD Equity Ownership/Stock Options: Pfizer [Anticoagulants]. All of the relevant financial relationships listed have been mitigated. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Scott E Kasner, MD Grant/Research/Clinical Trial Support: Bayer [Stroke]; Bristol Meyers Squibb [Stroke]; Medtronic [Stroke]; WL Gore and Associates [Stroke]. Consultant/Advisory Boards: Abbvie [Stroke]; AstraZeneca [Stroke]; BMS [Stroke]; Diamedica [Stroke]; Medtronic [Stroke]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. John F Dashe, MD, PhD No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 34/34