ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Stroke in patients with atrial fibrillation

Stroke in patients with atrial fibrillation
Literature review current through: Jan 2024.
This topic last updated: Jul 21, 2023.

INTRODUCTION — An ischemic stroke may occur in patients with atrial fibrillation (AF) either as the initial presenting manifestation of AF or despite appropriate antithrombotic prophylaxis. In such patients, a cardiac embolus, most commonly a thrombus originating from the left atrial appendage (LAA), is the cause of the ischemic stroke. (See "Clinical diagnosis of stroke subtypes", section on 'Brain ischemia'.)

Issues specific to stroke in patients with AF will be reviewed here. The risk of atheroembolism (including stroke), the role of anticoagulant prophylaxis (primary prevention) in patients with AF, and the general evaluation and management of the patient with stroke are presented elsewhere. (See "Atrial fibrillation in adults: Use of oral anticoagulants" and "Overview of the evaluation of stroke" and "Approach to reperfusion therapy for acute ischemic stroke" and "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack".)

STROKE CHARACTERISTICS — Strokes due to embolization of thrombus, most commonly from the left atrial appendage (LAA) in patients with AF, present with the characteristics of ischemic stroke. (See "Clinical diagnosis of stroke subtypes", section on 'Distinguishing stroke subtypes'.)

Features suggestive of cardioembolic stroke

Increased clinical severity – AF is associated with more severe ischemic strokes and "longer" transient ischemic attacks (TIAs) than emboli from carotid disease, presumably due to embolization of larger thrombi with AF [1,2]. This relationship was illustrated in a report comparing ischemic brain events in patients with AF with those with carotid disease in two major trials. The ratio of hemispheric events to retinal events was 25:1 with AF compared with 2:1 with carotid disease [1]. As a result, patients with AF who suffer an ischemic stroke appear to have a worse outcome (more disability, greater mortality) than those who have an ischemic stroke in the absence of AF, even after adjustment for the advanced age of patients with AF-related stroke [3-5]. The "longer" TIAs typical in AF patients are more often associated with abnormal magnetic resonance diffusion imaging and would be classified as strokes by the revised American Heart Association definition [6]. (See "Definition, etiology, and clinical manifestations of transient ischemic attack".)

Radiologic patterns – Cardioembolic stroke from AF may affect any vascular territory or multiple vascular territories of the brain with one or more wedge-shaped infarcts involving the cortex and the underlying subcortical white matter. Other patterns include striatocapsular infarction from a middle cerebral artery stem occlusion and/or borderzone infarcts [7].

Silent cerebral infarction — In addition to causing symptomatic stroke with major deficits, AF is also associated with silent cerebral infarctions (SCIs) and TIA [8-13]. SCI is characterized by brain lesions that have a radiographic appearance consistent with cerebral infarction in the absence of clinical complaints or findings. In a 2014 systematic review and meta-analysis of 17 studies, the prevalence of SCI lesions on magnetic resonance imaging and computed tomography among patients with AF was 40 and 22 percent, respectively [12]. In this review, AF was associated with more than a twofold increased risk of SCI in patients with no history of symptomatic stroke (odds ratio 2.62, 95% CI 1.81-3.80) in 11 studies. However, most studies pooled in this meta-analysis were cross-sectional, making the causal link between AF and silent cerebral infarction uncertain.

ACUTE ISCHEMIC STROKE — The initial rapid evaluation of acute ischemic stroke for patients with known or suspected AF is similar to the approach for patients with other known or suspected causes of stroke.

Is reperfusion therapy indicated? — All patients with acute ischemic stroke should be evaluated for possible reperfusion therapy, including urgent brain and neurovascular imaging. The immediate goal of reperfusion therapy is to restore blood flow to the regions of brain that are ischemic but not yet infarcted. (See "Approach to reperfusion therapy for acute ischemic stroke".)

Intravenous thrombolysis (IVT) improves functional outcome at three to six months when given within 4.5 hours of ischemic stroke onset. (See "Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic use".)

However, contraindications to IVT may be relevant for patients with AF and acute ischemic stroke (table 1):

Current vitamin K antagonist (VKA) use (eg, warfarin) with evidence of anticoagulant effect (eg, an international normalized ratio [INR] >1.7 or prothrombin time >15 seconds).

Direct-acting oral anticoagulant (DOAC; also referred to as non-vitamin K oral anticoagulants [NOAC]) use, unless the patient has not received a DOAC dose for more than 48 hours, assuming normal renal function or laboratory tests such as partial thromboplastin time, INR, platelet count, ecarin clotting time, thrombin time, or appropriate direct factor Xa activity assays are normal. In most cases, only the INR is readily available for clinical decision-making.

Evidence of intracranial hemorrhage on neuroimaging.

Mechanical thrombectomy is indicated for select patients with acute ischemic stroke caused by an intracranial large artery occlusion in the proximal anterior circulation who can be treated within 24 hours of the time last known to be well (algorithm 1). (See "Mechanical thrombectomy for acute ischemic stroke".)

Specific data on the effectiveness of thrombolytic therapy in ischemic stroke are limited for patients with AF, although such patients account for 20 to 30 percent of those participating in clinical trials [14,15]. As an example, the National Institute of Neurological Disorders and Stroke (NINDS) trial included 115 patients with AF (18 percent) [14]. No subgroup analysis of these patients has been reported, although there was no evidence of a treatment interaction between history of AF and benefit from alteplase. The large size and worse prognosis of AF-associated acute ischemic stroke accentuate both the risks and the benefits of fibrinolysis [15]. (See "Approach to reperfusion therapy for acute ischemic stroke".)

Diagnostic approach

Comprehensive evaluation — Patients with AF who suffer an ischemic stroke are likely to have had a cardioembolic event. On the other hand, AF is common in older adults, who often are at risk for other types of stroke. Thus, the presence of AF in a stroke patient does not always mean that there is a causal relationship [16]. As a result, all patients with a stroke, even in the setting of AF, need a complete evaluation for other causes of stroke, especially if they would result in different treatment.

The evaluation is generally the same as the evaluation in other patients with acute stroke, including brain and neurovascular imaging, cardiac rhythm monitoring during the acute phase, and echocardiography. As for other patients with a suspected embolic stroke, transesophageal echocardiography (TEE) may be used to identify embolic sources (intracardiac or aortic), which may be particularly helpful for patients at increased risk for complications of anticoagulation. However, a TEE is not used to exclude AF as the cause of embolic stroke, since residual atrial thrombi may or may not be present. (See "Overview of the evaluation of stroke", section on 'Ischemia' and "Overview of the evaluation of stroke", section on 'Confirming the diagnosis'.)

Source of embolism — For those patients with AF in whom an embolic stroke seems likely, other sources than the left atrial appendage (LAA) need to be considered. Embolism refers to particles of debris originating elsewhere that block arterial access to a particular brain region. Embolic strokes may arise from a source in the heart, aorta, or large vessels (table 2). (See "Stroke: Etiology, classification, and epidemiology", section on 'Embolism' and "Clinical diagnosis of stroke subtypes", section on 'Brain ischemia'.)

Thromboembolism of aortic atheroma is discussed separately. (See "Thromboembolism from aortic plaque".)

Brain and neurovascular imaging — Neuroimaging should be obtained for all patients suspected of having acute ischemic stroke or transient ischemic attack (TIA). Brain and neurovascular imaging play an essential role in acute stroke by:

Differentiating ischemia from hemorrhage

Excluding stroke mimics, such as tumor

Assessing the status of large cervical and intracranial arteries

Estimating the volume of brain tissue that is irreversibly infarcted (ie, infarction "core")

Estimating the extent of potentially salvageable brain tissue that is at risk for infarction (ie, ischemic "penumbra")

Guiding acute interventions, including patient selection for reperfusion therapies (ie, intravenous thrombolysis and mechanical thrombectomy)

Imaging of acute ischemic stroke is reviewed in detail elsewhere. (See "Neuroimaging of acute stroke".)

Cardiac monitoring — For patients in sinus rhythm without a history of AF, cardiac rhythm monitoring is recommended for at least the first 24 to 48 hours after the onset of ischemic stroke to identify AF or atrial flutter [17]. However, paroxysmal AF may not be detected on short-term cardiac monitoring such as continuous telemetry and 24- or 48-hour Holter monitors. To increase the likelihood of detecting AF, ambulatory cardiac monitoring for several weeks is suggested for all adult patients with a cryptogenic ischemic stroke or cryptogenic TIA. (See "Overview of the evaluation of stroke", section on 'Monitoring for subclinical atrial fibrillation'.)

Echocardiography — Transthoracic echocardiographic (TTE) evaluation is recommended for most patients presenting with ischemic stroke, primarily to investigate the conditions associated with AF. Because chronic anticoagulation with warfarin or one of the DOACs is recommended in all eligible patients with AF and stroke, echocardiography often will not have a significant impact on anticoagulant management decisions. (See "Role of echocardiography in atrial fibrillation" and "Epidemiology, risk factors, and prevention of atrial fibrillation" and "Atrial fibrillation in adults: Use of oral anticoagulants".)

The LAA and thus LAA thrombus are rarely seen on TTE but are easily visualized/detected by TEE. Approximately 45 percent of patients presenting with an acute embolic event in the setting of new-onset AF will have residual LAA thrombus [18,19]. Even when not seen on TEE, an intracardiac thrombus is presumed to have been present in all patients with AF who have had a recent thromboembolic event independent of anticoagulation status. This hypothesis is based in part upon the observations that microscopic thrombus can be identified in most patients with chronic sustained AF at autopsy [20] and that patients with a recent thromboembolism and newly recognized AF are significantly more likely to have spontaneous echocardiography contrast (a marker of stasis) than similar patients without a thromboembolic event (87 versus 48 percent) [19].

Thus, for patients with AF, diagnostic evaluation by TEE to search for a residual intraatrial thrombus is not essential since the absence of a thrombus will not alter the long-term clinical (anticoagulation) management. However, TEE to confirm absence of residual thrombus prior to cardioversion may be reasonable for those in whom a rhythm strategy is going to be pursued. (See "Role of echocardiography in atrial fibrillation" and "Management of atrial fibrillation: Rhythm control versus rate control".)

Managing antithrombotic therapy acutely

Stop anticoagulation temporarily – For most patients on anticoagulant therapy at the time of stroke onset, anticoagulation is temporarily withheld during the acute phase of ischemic stroke due to the risk of hemorrhagic transformation of the brain infarction.

Acute antiplatelet therapy – In patients with AF who experience an ischemic stroke, 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 [21,22]. These benefits must be balanced against the risk of intracranial bleeding with antithrombotic therapy.

Starting or resuming oral anticoagulation – Once the stroke evaluation is complete, antithrombotic therapy may be modified according to the ischemic stroke mechanism (algorithm 3). For patients with AF, long-term oral anticoagulation is started (or resumed) once the risk of hemorrhagic transformation has diminished, usually within the first days to two weeks after stroke onset, as guided mainly by the size of the ischemic infarct. (See 'Timing after acute ischemic stroke' below.)

The management of acute antithrombotic therapy in patients with stroke is discussed in detail elsewhere. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack".)

RISK OF RECURRENT STROKE — Patients who have had a prior embolic event already have the most potent risk factor for subsequent stroke. The risk of recurrent stroke in the first few weeks after the initial event is 3 to 5 percent based upon large numbers of patients observed in the control arms of randomized trials [21,22]. In addition, a risk of up to 12 percent per year has been reported in nonanticoagulated patients in the first two to three years after a stroke [23,24].

Due to the high risk of recurrent embolism, lifelong anticoagulation is recommended for secondary prevention (these patients have a minimum CHA2DS2-VASc score (calculator 1) of 2 for which chronic anticoagulation is strongly recommended).

LONG-TERM ANTICOAGULATION

Indications — For most patients with ischemic stroke and AF, chronic oral anticoagulation is recommended to reduce the risk of thromboembolism and recurrent ischemic stroke, independent of the cause of the stroke.

Patients with a previous intracranial hemorrhage may be candidates for anticoagulation, depending upon their risk of recurrent ischemic stroke and intracranial bleeding. (See "Spontaneous intracerebral hemorrhage: Secondary prevention and long-term prognosis", section on 'Anticoagulation'.)

Benefit — Randomized trials have shown that therapeutic oral anticoagulant with a vitamin K antagonist (VKA) or a direct-acting oral anticoagulant (DOAC) reduces the risk of ischemic stroke and other embolic events by approximately two-thirds compared with placebo irrespective of baseline risk. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation", section on 'General efficacy'.)

DOACs – Randomized trials have demonstrated that DOACs are either superior (apixaban and dabigatran) or noninferior (edoxaban or rivaroxaban) to VKAs for stroke prevention. Studies have also shown that DOACs have less bleeding side effects than VKAs among patients with AF and ischemic stroke or transient ischemic attack (TIA). DOACS are also preferred over VKAs for patients with AF and other indications for anticoagulation. (See "Atrial fibrillation in adults: Use of oral anticoagulants".)

In the ARISTOTLE trial, among 3436 participants with stroke or systemic embolism, apixaban was found to be superior to adjusted-dose warfarin in preventing recurrent stroke or systemic embolism (2.5 versus 3.2 percent; hazard ratio [HR] 0.79, 95% CI 0.66-0.95) [25]. Apixaban also caused less major bleeding compared with warfarin (2.1 versus 3.1 percent; HR 0.69, 95% CI 0.60-0.80) and resulted in lower overall mortality (3.5 versus 3.9 percent). In a separate trial, among patients with prior stroke, dabigatran had a larger protective effect on stroke as compared with warfarin but had similar rates of major hemorrhage [26]. In other clinical trials of patients with prior stroke or TIA, both edoxaban [27] and rivaroxaban [28] were found to be noninferior to warfarin with respect to future stroke prevention.

WarfarinAspirin alone offers inadequate protection, with a stroke risk that averaged 10 percent per year in a pooled analysis of individual participants from six randomized trials [29]. Compared with aspirin, treatment with adjusted-dose warfarin (international normalized ratio 2 to 3) reduced this risk to 4 percent per year.

In an analysis from the EAFT and SPAF III trials of 834 patients with prior nondisabling ischemic stroke or prior TIA at study entry, the long-term risk of recurrent stroke was lower in patients with a prior TIA than in those with a prior ischemic stroke [30]. However, the reduction in recurrent stroke risk with warfarin therapy was comparable in both groups: 3 versus 7 percent per year with aspirin in patients with a TIA and 4 versus 11 percent per year in those with ischemic stroke.

In addition, anticoagulated patients with AF who experience ischemic stroke typically have smaller infarcts with a lower mortality rate compared with patients with AF and stroke who are not anticoagulated [31,32]. This is likely explained by a higher fraction of nonembolic strokes among anticoagulated AF patients and small size of embolic strokes. Anticoagulation greatly reduced the likelihood of large stroke due to left atrial emboli, so that the remaining strokes are from cerebral small artery disease or other mechanisms [31].

Risk — The most feared complication of anticoagulant therapy is the risk of major bleeding, as reviewed separately. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation", section on 'Bleeding risk' and "Risks and prevention of bleeding with oral anticoagulants".)

The decision of whether to use chronic oral anticoagulants must take both benefit and risk into account through shared decision-making with the patient. However, the benefit of oral anticoagulants far outweighs the risk for nearly all patients with ischemic stroke and AF [33]. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation".)

Choosing between direct-acting oral anticoagulants and warfarin — For most patients with stroke or TIA and AF who do not have a specific indication for warfarin or another VKA, a DOAC is preferred to a VKA. (See "Atrial fibrillation in adults: Use of oral anticoagulants" and "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Approach to anticoagulation'.)

Situations where a VKA is indicated (rather than a DOAC) include the following [33]:

Moderate to severe mitral stenosis

Mechanical heart valve in any location

Warfarin is generally preferred for patients with severely impaired kidney function, since all DOACs are excreted by the kidney to some degree. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects", section on 'Chronic kidney disease'.)

Dosing — Dosing recommendations for DOACs (table 3) are reviewed in detail elsewhere. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects".)

Note that there are legitimate reasons for DOAC dose reductions, which differ according to the specific agent. In general, clinical settings in which dose modification may be indicated include older age, low body weight, renal insufficiency, and/or concomitant use of interacting drugs. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects".)

For patients with AF treated with a VKA (eg, warfarin), an INR between 2 and 3 is recommended, with an average annual time in the therapeutic range >70 percent. (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Vitamin K antagonist'.)

Timing after acute ischemic stroke — For medically stable patients with AF and a small- or moderate-sized infarct with no intracranial bleeding, warfarin can be initiated soon (after 24 hours) after admission with minimal risk of transformation to hemorrhagic stroke. We prefer to wait 48 hours to start a DOAC in these patients, as DOACs have a more rapid anticoagulant effect.

Withholding anticoagulation for one to two weeks is generally recommended for those with large ischemic stroke, symptomatic hemorrhagic transformation, or poorly controlled hypertension [34-38]. Patients may benefit from aspirin until therapeutic anticoagulation is achieved [39]. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack".)

Although once widely practiced, early treatment with heparin for patients with AF who have an acute cardioembolic stroke should generally be avoided, as studies have shown that such treatment causes more harm than good. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack", section on 'Atrial fibrillation'.)

Specific patient groups

Patients with another potential stroke mechanism — In some patients with ischemic stroke and AF, the work-up will identify a noncardioembolic stroke mechanism (eg, large artery atherosclerosis, small vessel disease, other determined etiology) as the potential cause of the stroke.

Lacunar infarction – The optimal therapy is not known for patients with AF who experience a small subcortical "lacunar" infarct deemed as likely to be due to cerebral small artery disease as opposed to a cardiac embolus [40]. Anticoagulation is recommended for these patients even though the stroke mechanism is uncertain. This is because in randomized trials, these patients would have been categorized as having a history of stroke; these trials have consistently shown that patients with a history of stroke benefit from VKA and DOACs.

Large artery stenosis – Some patients with AF have a significant ipsilateral stenosis of a large artery that supplies the territory of the acute ischemic stroke. In such cases, it is usually impossible to determine with certainty which mechanism was causative. Anticoagulation for AF is recommended, and the large artery stenosis should be treated appropriately (eg, revascularization for cervical internal carotid artery stenosis) as a separate cause.

Older age — Older age is generally cited as a risk factor for bleeding; the risk increase with age is approximately linear. However, the risk of bleeding attributable to older age is often overestimated, and anticoagulants are underused in older individuals who are at the highest risk of stroke and may derive more benefit than younger individuals [33]. (See "Risks and prevention of bleeding with oral anticoagulants", section on 'Age, race, and sex'.)

Fall risk — Among patients with a history of falls or at high risk of falling, the risk of intracranial hemorrhage is increased among patients on anticoagulation, aspirin, or no antithrombotic therapy, but the absolute increased risk of intracranial hemorrhage related to anticoagulation is small. In particular, anticoagulation increases the risk of subdural hemorrhage (SDH), which is often due to falls, but the absolute risk with VKA therapy is approximately two additional SDHs per 1000 patients [41], which is much lower compared with the risk of cardioembolic stroke due to AF [33].

Nonrandomized studies suggest that for patients with AF and high risk of falls, the benefit of anticoagulation (ie, a reduced risk of ischemic stroke and consequent disability) outweighs the risk of intracranial bleeding from a fall. (See "Risks and prevention of bleeding with oral anticoagulants", section on 'Risk factors for bleeding in specific sites'.)

Anticoagulant-intolerant patients — Left atrial appendage (LAA) occlusion or dual antiplatelet therapy may be reasonable alternatives to therapy with aspirin alone in high-risk patients with AF who cannot be treated with long-term warfarin or DOAC, or because of strong patient preference following careful consideration of the advantages of oral anticoagulation.

LAA occlusion is discussed separately. (See "Atrial fibrillation: Left atrial appendage occlusion".)

ANTICOAGULATION FAILURE

Determining the cause of recurrent stroke — All patients with AF who have an ischemic stroke despite oral anticoagulation with a vitamin K antagonist (VKA) or a direct-acting oral anticoagulant (DOAC) should have a thorough evaluation to determine if the most likely stroke mechanism is cardioembolic due to AF or noncardioembolic due to large artery atherosclerosis, small vessel disease, or another cause of ischemic stroke. Note that patients with ischemic stroke and AF will still need chronic oral anticoagulation even if a competing stroke mechanism is found.

Transesophageal echocardiogram (TEE) is useful to assess for left atrial appendage (LAA) thrombus and other potential cardiac sources of embolism. (See "Overview of the evaluation of stroke", section on 'Ischemia' and "Overview of the evaluation of stroke", section on 'Confirming the diagnosis'.)

Missed doses should be suspected in patients taking a DOAC, and subtherapeutic intensity of anticoagulation is a very common cause of treatment failure for patients taking a VKA [42-44]. For patients with stroke on DOACs with good compliance or while on warfarin anticoagulation with a therapeutic international normalized ratio (INR), a noncardioembolic stroke mechanism (eg, lacunar, large artery stenosis, malignancy) is often the cause, although cardioembolism may account for the majority [44,45].

In an analysis of patients with ischemic stroke despite oral anticoagulation, the stroke etiology for 1674 patients taking a DOAC was due to the following factors [44]:

Cardioembolism - 49 percent

Poor adherence or insufficient dose – 23 percent

A competing mechanism – 28 percent

For 1274 patients taking a VKA, the stroke etiology was due to the following factors [44]:

Cardioembolism – 37 percent

Poor adherence or insufficient dose – 43 percent

A competing mechanism – 20 percent

Direct-acting oral anticoagulant treatment failure — While data are limited, ischemic stroke that occurs during therapy with a DOAC (eg, apixaban, dabigatran, edoxaban, or rivaroxaban) for AF has been associated with several factors, including treatment at doses lower than recommended and/or poor adherence. LAA thrombus, if present, suggests the need to reassess dosing and compliance. One study compared 713 cases of ischemic stroke or transient ischemic attack (TIA) during DOAC treatment with unmatched controls (consecutive outpatients with AF) who did not have cerebrovascular events during DOAC treatment [46]. In multivariable analysis, ischemic cerebrovascular events were associated with off-label under-dosing of DOAC, atrial enlargement, hyperlipidemia, and higher CHA2DS2-VASc score.

It is important to verify that the correct DOAC dose was prescribed and that the patient was compliant. If a thrombus is present despite appropriate dosing and compliance, it is reasonable to change to another DOAC, but optimal treatment is uncertain, and no consensus exists. A retrospective study suggested that for patients with left ventricular thrombus, warfarin may be superior to DOAC for reducing the risk of stroke or systemic embolism [47]. Analogous data for AF patients with LAA thrombi are not available.

Regardless, resuming oral anticoagulation therapy for patients with AF is generally indicated after one to two weeks of temporary interruption with large infarcts or shorter interruption with small infarcts.

Warfarin treatment failure — In patients with AF who suffer ischemic stroke during warfarin anticoagulation, the intensity of anticoagulation is most often subtherapeutic (INR less than 2), and continuing warfarin after one to two weeks of temporary interruption for patients with large infarcts or shorter interruption with small infarcts with renewed efforts to keep the INR in the 2 to 3 therapeutic range or consideration of a change to a DOAC is advised.

When ischemic stroke occurs with a therapeutic INR (2 to 3), we favor increasing the target INR to 2.5 to 3.5, or switching from warfarin to a DOAC rather than routine addition of antiplatelet therapy. The addition of antiplatelet therapy is known to increase major hemorrhage (and particularly brain hemorrhage), and the benefit is less well defined.

HEMORRHAGIC STROKE — For patients with AF 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 management issues are discussed separately.(See "Reversal of anticoagulation in intracranial hemorrhage" and "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis".)

ADDITIONAL SECONDARY PREVENTION STRATEGIES

Early rhythm control – One trial suggested a benefit of early rhythm control among patients with AF who had a stroke [48]. In this study, 300 patients with AF and acute ischemic stroke were randomly assigned to early rhythm control or usual care. The rate of ischemic stroke was lower in the rhythm control group at 12 months (1.7 versus 6.3 percent); rates of mortality and hospitalizations did not differ. Rates of sustained AF were lower in the early rhythm control group compared with usual care (34 versus 63 percent) at 12 months. A potential limitation of this study was that it was non-blinded. Further randomized studies in other populations are needed before we can recommend the widespread use of early rhythm control in patients with stroke and AF.

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 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.)

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 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".)

  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. Jørgensen HS, Nakayama H, Reith J, et al. Acute stroke with atrial fibrillation. The Copenhagen Stroke Study. Stroke 1996; 27:1765.
  5. Lamassa M, Di Carlo A, Pracucci G, et al. Characteristics, outcome, and care of stroke associated with atrial fibrillation in Europe: data from a multicenter multinational hospital-based registry (The European Community Stroke Project). Stroke 2001; 32:392.
  6. Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke 2009; 40:2276.
  7. Sachdeva G, Saeed A, Jani V, Razak A. Radiological Portrait of Embolic Strokes. Cardiol Clin 2016; 34:269.
  8. Ezekowitz MD, James KE, Nazarian SM, et al. Silent cerebral infarction in patients with nonrheumatic atrial fibrillation. The Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. Circulation 1995; 92:2178.
  9. Kempster PA, Gerraty RP, Gates PC. Asymptomatic cerebral infarction in patients with chronic atrial fibrillation. Stroke 1988; 19:955.
  10. Cullinane M, Wainwright R, Brown A, et al. Asymptomatic embolization in subjects with atrial fibrillation not taking anticoagulants: a prospective study. Stroke 1998; 29:1810.
  11. Das RR, Seshadri S, Beiser AS, et al. Prevalence and correlates of silent cerebral infarcts in the Framingham offspring study. Stroke 2008; 39:2929.
  12. Kalantarian S, Ay H, Gollub RL, et al. Association between atrial fibrillation and silent cerebral infarctions: a systematic review and meta-analysis. Ann Intern Med 2014; 161:650.
  13. Rydén L, Sacuiu S, Wetterberg H, et al. Atrial Fibrillation, Stroke, and Silent Cerebrovascular Disease: A Population-based MRI Study. Neurology 2021; 97:e1608.
  14. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995; 333:1581.
  15. Hart RG, Palacio S, Pearce LA. Atrial fibrillation, stroke, and acute antithrombotic therapy: analysis of randomized clinical trials. Stroke 2002; 33:2722.
  16. Hart RG, Pearce LA, Miller VT, et al. Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies. Cerebrovasc Dis 2000; 10:39.
  17. 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.
  18. Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Ann Intern Med 1998; 128:639.
  19. Manning WJ, Silverman DI, Waksmonski CA, et al. Prevalence of residual left atrial thrombi among patients with acute thromboembolism and newly recognized atrial fibrillation. Arch Intern Med 1995; 155:2193.
  20. Fisher, CM. Embolism in atrial fibrillation. In: Atrial Fibrillation, Kulbertus, HE, Olsson, SB, Schlepper, M (Eds), Alindgren & Soner AB, Moindal, Sweden 1981. p.192.
  21. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet 1997; 349:1569.
  22. Saxena R, Lewis S, Berge E, et al. Risk of early death and recurrent stroke and effect of heparin in 3169 patients with acute ischemic stroke and atrial fibrillation in the International Stroke Trial. Stroke 2001; 32:2333.
  23. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. EAFT (European Atrial Fibrillation Trial) Study Group. Lancet 1993; 342:1255.
  24. Sandercock P, Bamford J, Dennis M, et al. Atrial fibrillation and stroke: prevalence in different types of stroke and influence on early and long term prognosis (Oxfordshire community stroke project). BMJ 1992; 305:1460.
  25. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365:981.
  26. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361:1139.
  27. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369:2093.
  28. Hankey GJ, Patel MR, Stevens SR, et al. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF. Lancet Neurol 2012; 11:315.
  29. van Walraven C, Hart RG, Singer DE, et al. Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis. JAMA 2002; 288:2441.
  30. Hart RG, Pearce LA, Koudstaal PJ. Transient ischemic attacks in patients with atrial fibrillation: implications for secondary prevention: the European Atrial Fibrillation Trial and Stroke Prevention in Atrial Fibrillation III trial. Stroke 2004; 35:948.
  31. Hylek EM, Go AS, Chang Y, et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 2003; 349:1019.
  32. Rizos T, Meid AD, Huppertz A, et al. Low Exposure to Direct Oral Anticoagulants Is Associated with Ischemic Stroke and Its Severity. J Stroke 2022; 24:88.
  33. Best JG, Bell R, Haque M, et al. Atrial fibrillation and stroke: a practical guide. Pract Neurol 2019; 19:208.
  34. Paciaroni M, Agnelli G, Ageno W, Caso V. Timing of anticoagulation therapy in patients with acute ischaemic stroke and atrial fibrillation. Thromb Haemost 2016; 116:410.
  35. Smythe MA, Parker D, Garwood CL, et al. 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.
  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. Factors associated with therapeutic anticoagulation status in patients with ischemic stroke and atrial fibrillation. J Stroke Cerebrovasc Dis 2020; 29:104888.
  44. Polymeris AA, Meinel TR, Oehler H, et al. Aetiology, secondary prevention strategies and outcomes of ischaemic stroke despite oral anticoagulant therapy in patients with atrial fibrillation. J Neurol Neurosurg Psychiatry 2022; 93:588.
  45. Freedman B, Martinez C, Katholing A, Rietbrock S. Residual Risk of Stroke and Death in Anticoagulant-Treated Patients With Atrial Fibrillation. JAMA Cardiol 2016; 1:366.
  46. Paciaroni M, Agnelli G, Caso V, et al. Causes and Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation Treated With Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention. Stroke 2019; 50:2168.
  47. Robinson AA, Trankle CR, Eubanks G, et al. Off-label Use of Direct Oral Anticoagulants Compared With Warfarin for Left Ventricular Thrombi. JAMA Cardiol 2020; 5:685.
  48. Park J, Shim J, Lee JM, et al. Risks and Benefits of Early Rhythm Control in Patients With Acute Strokes and Atrial Fibrillation: A Multicenter, Prospective, Randomized Study (the RAFAS Trial). J Am Heart Assoc 2022; 11:e023391.
  49. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358:1033.
  50. Arima H, Hart RG, Colman S, et al. Perindopril-based blood pressure-lowering reduces major vascular events in patients with atrial fibrillation and prior stroke or transient ischemic attack. Stroke 2005; 36:2164.
  51. Flint AC, Conell C, Ren X, et al. Statin Adherence Is Associated With Reduced Recurrent Stroke Risk in Patients With or Without Atrial Fibrillation. Stroke 2017; 48:1788.
Topic 1059 Version 50.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟