11/49 7/5/23, 12:10 PM Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack - UpToDate examined the effect of anticoagulant therapy versus control in the early treatment of patients with acute ischemic stroke [37]. This review included 28 trials involving 24,025 subjects; approximately 80 percent of the subjects were from the IST trial. There was considerable variation in the quality of the trials. The anticoagulants tested were standard unfractionated heparin, low molecular weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. The following were the major findings [37]: Anticoagulant therapy did not reduce the risk of death from all causes (odds ratio [OR] 0.99, 95% CI 0.90-1.09). Anticoagulants did not reduce the risk of being dead or dependent at the end of follow- up (OR 0.98, 95% CI 0.92-1.03). Anticoagulants reduced the odds of recurrent ischemic stroke (OR 0.75, 95% CI 0.65-0.88) but increased the risk of symptomatic intracranial hemorrhage (OR 2.99, 95% CI 2.24-3.99). Uncertain benefit for large vessel atherosclerotic disease Clinical trials have not adequately evaluated adjusted intravenous anticoagulation in patients with selected stroke subtypes. With this caveat in mind, there are conflicting data regarding the benefit of intravenous unfractionated heparin or low molecular weight heparin in the subgroup of patients with large vessel atherosclerotic disease. Note that these trials included many patients with minor ischemic stroke who would now be treated with short-term DAPT, but the comparator at the time was aspirin monotherapy. The TOAST trial evaluated the efficacy of the low molecular weight heparinoid danaparoid administered as an intravenous bolus within 24 hours of symptom onset and continued for seven days in 1281 patients with acute ischemic stroke [35]. Compared with placebo, danaparoid was associated with no improvement in overall outcome at three months (75 versus 74 percent rates of favorable outcome). However, subgroup analysis suggested a higher rate of favorable outcomes in patients treated with danaparoid who had a large artery atherosclerotic stroke (68 versus 55 percent with placebo). The FISS-tris trial evaluated the low molecular weight heparin nadroparin (3800 anti- factor Xa international units, 0.4 mL subcutaneously twice daily) versus aspirin (160 mg once daily) started within 48 hours of acute ischemic stroke onset and continued for 10 days [38]. The main study population was 353 patients with confirmed large artery occlusive disease, consisting of 300 with intracranial, 11 with extracranial, and 42 with both intracranial and extracranial disease. The mean time to treatment was nearly 30 hours. There was no significant difference between treatment with nadroparin or https://www.uptodate.com/contents/early-antithrombotic-treatment-of-acute-ischemic-stroke-and-transient-ischemic-attack/print 12/49 7/5/23, 12:10 PM Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack - UpToDate aspirin for the proportion of patients with good outcome at six months, defined by a table 4) score of 85 (73 versus 69 percent). However, there was a Barthel Index ( significant benefit to low molecular weight heparin in a prespecified secondary outcome measure, good outcome defined by a modified Rankin Scale ( table 5) score of 0 to 1 (54 versus 44 percent; OR 1.55, 95% CI 1.02-2.35). Contraindications Anticoagulation in the setting of acute stroke may only be considered after a brain imaging study has excluded hemorrhage and estimated the size of the infarct. Early anticoagulation should be avoided when potential contraindications to anticoagulation are present, such as a large infarction (based upon clinical syndrome or brain imaging findings); severe uncontrolled, persistent hypertension (eg, systolic blood pressure 185 or diastolic blood pressure 110 mmHg); symptomatic hemorrhagic infarction; or other bleeding conditions. Although there is no standard definition, many stroke experts consider "large" infarcts to be those that involve more than one-third of the middle cerebral artery territory or more than one- half of the posterior cerebral artery territory based upon neuroimaging with computed tomography (CT) or magnetic resonance imaging (MRI). Infarct size can also be clinically defined, but this process can underestimate the true infarct volume when so-called "silent" areas of association cortex are involved. Clinical estimation of infarct size may be improved by using validated scales that have been correlated with infarct volume and clinical outcome, such as the NIHSS ( table 3). As an example, one study found that an NIHSS score >15 was associated with a median infarct volume 3 of 55.8 cm and worse outcome than NIHSS scores of 1 to 7 (median infarct volume of 7.9 cm ) 3 3 or 8 to 15 (median infarct volume of 31.4 cm ) [39]. Thus, patients with an NIHSS score >15 generally have a large infarct. However, it should be recognized that part of the clinical deficit in the early hours of an acute stroke may be attributed to the penumbra, where the brain is ischemic but not infarcted. Additionally, NIHSS cutoffs may not apply equally well in both hemispheres. It is possible to have a relatively large infarct in the right hemisphere with a low NIHSS [40]. TREATMENT BY ISCHEMIC MECHANISM Once the evaluation for transient ischemic attack (TIA) or ischemic stroke is complete, antithrombotic therapy can be modified as necessary according to the ischemic mechanism ( algorithm 4 and algorithm 5). Cardioembolic source https://www.uptodate.com/contents/early-antithrombotic-treatment-of-acute-ischemic-stroke-and-transient-ischemic-attack/print 13/49 7/5/23, 12:10 PM Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack - UpToDate Atrial fibrillation While parenteral anticoagulation (eg, intravenous heparin) is generally not recommended for treating ischemic stroke in the acute period, oral anticoagulation with warfarin or a direct oral anticoagulant (DOAC) is recommended for secondary stroke prevention in patients with atrial fibrillation and other high-risk sources of cardiogenic embolism. (See "Stroke in patients with atrial fibrillation" and "Atrial fibrillation in adults: Use of oral anticoagulants".) The timing of oral anticoagulation initiation for such patients is mainly dependent on the size of the acute infarct and the presence of factors such as symptomatic hemorrhagic transformation and/or poorly controlled hypertension. Oral anticoagulation can be started immediately for patients with TIA due to atrial fibrillation and soon after onset for medically stable patients with a small- or moderate-sized infarct and no bleeding complications. For patients with large infarctions, symptomatic hemorrhagic transformation, or poorly controlled hypertension, withholding oral anticoagulation for one to two weeks is generally recommended [41]. (See 'Timing of long-term anticoagulation' below.) Although once widely practiced, early treatment with heparin for patients with atrial fibrillation who have an acute cardioembolic stroke causes more harm than good. A 2007 meta-analysis examined seven randomized controlled trials involving 4624 patients and compared heparin or low molecular weight heparins started within 48 hours for acute cardioembolic stroke with other treatments (aspirin or placebo) [42]. The following observations were reported: Parenteral anticoagulants led to a nonsignificant reduction in recurrent ischemic stroke within 7 to 14 days (3.0 versus 4.9 percent; OR 0.68, 95% CI 0.44-1.06) Parenteral anticoagulants led to an increase in symptomatic intracranial hemorrhage (2.5 versus 0.7 percent; OR 2.89, 95% CI 1.19-7.01) Parenteral anticoagulants and other treatments had a similar rate of death or disability at final follow-up (approximately 74 percent) These results do not support early parenteral anticoagulant treatment of acute cardioembolic stroke [42]. Anticoagulant failure Subtherapeutic anticoagulation intensity is often implicated when patients with atrial fibrillation present with TIA or ischemic stroke [43]. The first step should be to exclude an alternative ischemic mechanism unrelated to cardiogenic embolism. If ischemia is attributed to atrial fibrillation, an attempt should be made to identify and correct the cause (eg, inadequate compliance with anticoagulant therapy, drug/food interaction). Options include continuing warfarin (after temporary interruption if needed for acute ischemic stroke) with https://www.uptodate.com/contents/early-antithrombotic-treatment-of-acute-ischemic-stroke-and-transient-ischemic-attack/print 14/49 7/5/23, 12:10 PM Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack - UpToDate renewed efforts to keep the international normalized ratio (INR) in the 2 to 3 therapeutic range or switching to a DOAC. (See "Stroke in patients with atrial fibrillation", section on 'Anticoagulation failure' and "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Anticoagulant failure'.) Intracardiac thrombus Although benefit is unproven, we suggest early parenteral anticoagulation rather than aspirin only for select patients with acute cardioembolic ischemic stroke who are at high risk for short-term recurrent stroke due to intracardiac thrombus in the left ventricle or thrombus associated with mechanical or native heart valves. This approach is controversial; some experts favor treatment with aspirin rather than anticoagulation in this setting for patients with an acute brain infarction. Our suggestion to use early parenteral anticoagulation for these selected patients applies only to those with a small- to moderate-sized brain infarct and no evidence of hemorrhage on brain imaging. Anticoagulation should not be given for the first 24 hours following treatment with intravenous alteplase. Full-dose anticoagulation should not be used acutely for patients with a large infarction (based upon clinical syndrome or brain imaging findings), uncontrolled hypertension, or other bleeding conditions. (See 'Contraindications' above.) In the selected patients who receive heparin in the acute stroke setting, a bolus is not administered. One group has proposed a weight-based nomogram for heparin infusions that, compared with usual heparin therapy, is associated with fewer complications, fewer mistakes in dose adjustment, improved anticoagulation, and decreased nursing and house staff labor ( table 6) [44]. Enoxaparin 1 mg/kg dose every 12 hours (or other low molecular weight heparins) may be used as an alternative to intravenous heparin in patients with acute stroke when early anticoagulation is desired to prevent recurrent cerebral embolism; the limited available evidence suggests that low molecular weight heparins have similar efficacy, advantages in administration and monitoring, and reduced rates of thrombocytopenia compared with heparin. (See "Heparin and LMW heparin: Dosing and adverse effects", section on 'LMW heparin'.) Generally, patients with TIA or ischemic stroke attributed to an intracardiac thrombus should be transitioned to oral anticoagulation soon after initiation of parenteral anticoagulation. Oral anticoagulation is generally continued at least three months for left ventricular thrombus; concurrent antiplatelet therapy may be indicated for left ventricular thrombus after acute myocardial infarction. Chronic anticoagulation is indicated for patients with mechanical heart valves. (See "Left ventricular thrombus after acute myocardial infarction", section on 'Prevention of embolic events' and "Antithrombotic therapy for mechanical heart valves".) https://www.uptodate.com/contents/early-antithrombotic-treatment-of-acute-ischemic-stroke-and-transient-ischemic-attack/print 15/49 7/5/23, 12:10 PM Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack - UpToDate Noncardioembolic etiologies Antiplatelet therapy is the mainstay of secondary stroke prevention for patients with a noncardioembolic source of ischemic stroke. For most patients without atrial fibrillation or another indication for long-term oral anticoagulation, the antiplatelet regimen chosen at presentation can be continued: For patients with low-risk TIA or moderate to severe stroke, we recommend aspirin monotherapy (160 to 325 mg daily). (See 'Aspirin alone' above.) For patients with high-risk TIA or minor ischemic stroke, we recommend short-term dual antiplatelet therapy (DAPT) using aspirin and clopidogrel rather than aspirin alone. (See 'Short-term dual antiplatelet therapy (DAPT)' above.) After the acute period, treatment should continue with aspirin alone, clopidogrel alone, or aspirin-extended-release dipyridamole. (See "Long-term antithrombotic therapy for the secondary prevention of ischemic stroke".) However, modifications may apply for select stroke mechanisms: Extracranial internal carotid artery stenosis Patients with symptomatic internal carotid artery stenosis as the cause of TIA or ischemic stroke should be treated with early antiplatelet therapy. These patients generally benefit from carotid revascularization to reduce the risk of recurrent ipsilateral ischemic stroke. Aspirin monotherapy is preferred by some experts prior to carotid endarterectomy, while DAPT is preferred by others. DAPT is used prior to and continuing for 30 days after carotid artery stenting. (See "Carotid endarterectomy", section on 'Antiplatelet therapy' and "Overview of carotid artery stenting", section on 'Dual antiplatelet therapy'.) Intracranial large artery atherosclerosis For patients with a recent (within 30 days) TIA or ischemic stroke attributed to atherosclerotic intracranial large artery stenosis of 70 to 99 percent, DAPT with aspirin plus clopidogrel is used by some experts for up to 90 days. The use of antiplatelet therapy for patients with acute ischemic stroke due to intracranial large artery atherosclerosis is reviewed in detail separately. (See "Intracranial large artery atherosclerosis: Treatment and prognosis", section on 'Antiplatelet therapy'.) Dissection The use of antithrombotic therapy for ischemic stroke and TIA caused by cervical or intracranial artery dissection is discussed elsewhere. (See "Cerebral and cervical artery dissection: Treatment and prognosis", section on 'Choosing between antiplatelet and anticoagulation therapy'.) Other determined etiology Several conditions that are uncommon causes of TIA and ischemic stroke are discussed in detail separately: https://www.uptodate.com/contents/early-antithrombotic-treatment-of-acute-ischemic-stroke-and-transient-ischemic-attack/print 16/49 7/5/23, 12:10 PM Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack - UpToDate Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) Moyamoya disease and moyamoya syndrome: Treatment and prognosis Management of antiphospholipid syndrome Nonbacterial thrombotic endocarditis Cryptogenic Patients with cryptogenic TIA and ischemic stroke, including those with embolic stroke of undetermined source (ESUS), are generally treated with antiplatelet therapy while awaiting the results of long-term cardiac monitoring to look for atrial fibrillation as a possible cause of stroke. Thus, initial treatment involves aspirin monotherapy for low-risk TIA and moderate to severe ischemic stroke, or short-term DAPT for high-risk TIA and minor stroke. (See 'Indications for DAPT' above.) For long-term stroke prevention beyond the acute period, antiplatelet therapy with aspirin alone, clopidogrel alone, or aspirin-extended-release dipyridamole is recommended. (See "Long-term antithrombotic therapy for the secondary prevention of ischemic stroke".) Available data have shown no benefit from anticoagulation for secondary stroke prevention in patients with cryptogenic stroke or ESUS. The evaluation and management of cryptogenic stroke and ESUS is discussed in detail separately. (See "Cryptogenic stroke and embolic stroke of undetermined source (ESUS)".) OTHER TREATMENT ISSUES Hemorrhagic transformation and systemic bleeding For patients who develop severe systemic or intracranial bleeding complications, including symptomatic hemorrhagic transformation of the ischemic infarct, we withhold all anticoagulant and antiplatelet therapy for one to two weeks or until the patient is stable, at which time oral antiplatelet or anticoagulant treatment can be started or resumed as indicated. The development of asymptomatic hemorrhagic transformation of an ischemic infarct does not necessarily preclude the early use of antiplatelets, particularly when the hemorrhage is petechial (ie, scattered and punctate). In this setting, it is likely reasonable to continue aspirin. For asymptomatic parenchymal hematoma (ie, larger confluent bleeding within an infarct), it is not clear that stopping aspirin will have much impact on hematoma progression given the long- https://www.uptodate.com/contents/early-antithrombotic-treatment-of-acute-ischemic-stroke-and-transient-ischemic-attack/print 17/49 7/5/23, 12:10 PM Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack - UpToDate lasting effect of aspirin on platelet function, and it may be reasonable to continue aspirin, although management should be individualized. If antiplatelet therapy has not been started, it may be reasonable to delay initiation of antiplatelet therapy in patients with parenchymal hemorrhage until the patient's neurologic condition becomes stable. We avoid dual antiplatelet therapy (DAPT) in patients with hemorrhagic transformation, including those with petechial or parenchymal hemorrhage. Patients with another indication for chronic anticoagulation Some patients with acute ischemic stroke have indications other than atrial fibrillation or intracardiac thrombus for prolonged anticoagulation, such as acute coronary syndrome, prosthetic heart valve, or venous thromboembolism. In such cases, and in the absence of significant bleeding, we start aspirin if anticoagulation is delayed because of large infarction, high risk of symptomatic hemorrhagic transformation, and/or poorly controlled hypertension. We then stop aspirin once anticoagulation is started unless there is an indication for the use of concurrent antiplatelet therapy. (See 'Timing of long-term anticoagulation' below and 'Contraindications' above.) Venous thromboembolism prophylaxis Aspirin and other antiplatelet agents may be used to treat acute ischemic stroke when subcutaneous heparin or low molecular weight heparin is used for the prevention of venous thromboembolism. The prophylaxis of venous thromboembolism is discussed separately. (See "Prevention and treatment of venous thromboembolism in patients with acute stroke", section on 'Approach to VTE prevention'.) Swallowing difficulty Aspirin may be given rectally for patients with acute stroke who are nil per os (NPO) or those who have not had screening for dysphagia. Clopidogrel is available only as a tablet for oral administration. Timing of long-term anticoagulation There is no clear consensus about when to start or resume anticoagulation after acute ischemic stroke in patients with atrial fibrillation or another appropriate indication for anticoagulation. Different national guidelines have proposed different recommendations [41]. Based mainly on expert consensus, the timing of anticoagulation initiation for patients with an appropriate indication is mainly dependent on the size of the acute infarct and the presence of factors such as symptomatic hemorrhagic transformation and/or poorly controlled hypertension. The size of the infarction is presumed to correlate with the risk of hemorrhagic transformation. TIA For patients with a transient ischemic attack (TIA) and atrial fibrillation, oral anticoagulation can be started immediately. Small- to moderate-sized infarct For medically stable patients with a small- or moderate-sized infarct, warfarin can be initiated or restarted soon (eg, 24 hours) after https://www.uptodate.com/contents/early-antithrombotic-treatment-of-acute-ischemic-stroke-and-transient-ischemic-attack/print 18/49 7/5/23, 12:10 PM Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack - UpToDate admission with minimal risk of transformation to hemorrhagic stroke. We prefer to wait for 48 hours to start a DOAC, as DOACs have a more rapid anticoagulant effect. Large infarct For patients with large infarctions, symptomatic hemorrhagic transformation, or poorly controlled hypertension, withholding oral anticoagulation for one to two weeks is generally recommended [41]. Limited clinical trial data support earlier rather than later initiation of direct oral anticoagulants (DOACs) after ischemic stroke [45,46]. The open-label ELAN trial enrolled 2013 patients with atrial fibrillation and acute ischemic stroke [45]. Patients were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day six or seven after a major stroke) or later anticoagulation (day three or four after a minor stroke, day six or seven after a moderate stroke, or day 12 through 14 after a major stroke) using a DOAC. Stroke severity was determined by imaging size: an infarct of <1.5 cm was considered minor; an infarct in the distribution of a cortical superficial branch of the anterior, middle, or posterior cerebral artery was considered moderate; a larger infarct in the distributions of those arteries or an infarct >1.5 cm in the brainstem or cerebellum was considered major. The ELAN trial found a nonsignificant trend towards benefit with earlier anticoagulation [45]. At 30 days, the composite outcome (recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death) occurred in 29 participants in the early anticoagulation group compared with 41 in the later anticoagulant group (2.9 versus 4.1 percent, risk difference -1.18 percent, 95% CI -2.84 to 0.47). Recurrent ischemic stroke in the early and later groups occurred in 14 and 22 participants respectively (1.4 versus 2.5 percent, risk difference -1.14, 95% CI -2.41 to 0.13), while the rate of symptomatic intracranial hemorrhage was 0.2 percent in both groups. While not definitive, these findings suggest that early DOAC use is safe and may reduce the risk of recurrent ischemic stroke. Limitations to the ELAN trial include small number of events, a low median NIHSS score (3) at randomization, and exclusion of patients on therapeutic anticoagulation at baseline. For patients with atrial fibrillation in whom the start of anticoagulation will be delayed by more than 48 hours (eg, those with large acute infarction), we start aspirin as soon as possible after the diagnosis of transient ischemic attack (TIA) or ischemic stroke is confirmed if there are no significant bleeding complications; anticoagulation can be resumed according to indication (and aspirin stopped) according to the guidance above if the patient is stable. SOCIETY GUIDELINE LINKS https://www.uptodate.com/contents/early-antithrombotic-treatment-of-acute-ischemic-stroke-and-transient-ischemic-attack/print 19/49 7/5/23, 12:10 PM Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack - UpToDate Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Stroke (The Basics)") Beyond the Basics topics (see "Patient education: Stroke symptoms and diagnosis (Beyond the Basics)" and "Patient education: Ischemic stroke treatment (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Immediate treatment All patients with acute ischemic stroke should be evaluated to determine eligibility for reperfusion therapy with intravenous thrombolysis and/or mechanical thrombectomy ( algorithm 1), and aspirin and other antithrombotic agents should not be given alone or in combination for the first 24 hours following treatment with intravenous thrombolysis. (See 'Evaluate for reperfusion therapy' above and 'Start antiplatelets as soon as possible' above.) Otherwise, antiplatelet agents should be started as soon as possible after the diagnosis of transient ischemic attack (TIA) or ischemic stroke is confirmed, even before the evaluation for ischemic mechanism is complete. For most patients with no indication for long-term oral anticoagulation who have TIA ( algorithm 2) or ischemic stroke ( algorithm 3), we start antiplatelet therapy as follows (see 'Aspirin alone' above and 'Short-term dual antiplatelet therapy (DAPT)' above): https://www.uptodate.com/contents/early-antithrombotic-treatment-of-acute-ischemic-stroke-and-transient-ischemic-attack/print 20/49 7/5/23, 12:10 PM Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack - UpToDate Aspirin alone for low-risk TIA or moderate to severe ischemic stroke For patients 2 with a low-risk TIA, defined by an ABCD (for Age, Blood pressure, Clinical features, Duration of symptoms, and Diabetes) score <4 ( table 2), or moderate to major ischemic stroke, defined by a National Institutes of Health Stroke Scale (NIHSS) score >5 ( table 3), we start treatment with aspirin (162 to 325 mg daily) alone. DAPT for high-risk TIA or minor ischemic stroke For patients with a high-risk TIA, 2 defined by an ABCD score 4 ( table 2), or minor ischemic stroke, defined by an NIHSS score 5 ( table 3), we begin with dual antiplatelet therapy (DAPT) for 21 days using aspirin (160 to 325 mg loading dose, followed by 50 to 100 mg daily) plus clopidogrel (300 to 600 mg loading dose, followed by 75 mg daily) rather than aspirin alone. Aspirin and ticagrelor is an alternative DAPT regimen. Treatment by ischemic mechanism Once the evaluation for TIA or stroke is complete, early antithrombotic therapy can be modified if necessary ( algorithm 4 and algorithm 5) according to the ischemic mechanism (see 'Treatment by ischemic mechanism' above): Atrial fibrillation For patients with TIA or ischemic stroke who have atrial fibrillation, oral anticoagulation with warfarin or a direct oral anticoagulant (DOAC) is recommended for secondary stroke prevention (see "Stroke in patients with atrial fibrillation"). Oral anticoagulation can be started immediately for patients with TIA and soon after stroke onset for medically stable patients with a small- or moderate-sized infarct and no bleeding complications or uncontrolled hypertension. For patients with large infarctions, symptomatic hemorrhagic transformation, or poorly controlled hypertension, withholding oral anticoagulation for one to two weeks is generally advised. (See 'Atrial fibrillation' above and 'Timing of long-term anticoagulation' above.) Intracardiac thrombus For patients with acute cardioembolic TIA or ischemic stroke who have intracardiac thrombus in the left ventricle or associated with mechanical or native heart valves, we suggest early parenteral anticoagulation rather than aspirin (Grade 2C). This approach is controversial. (See 'Limited role of early anticoagulation' above.) Noncardioembolic etiologies For most patients without atrial fibrillation or another indication for long-term oral anticoagulation, the antiplatelet regimen chosen at presentation can be continued: for patients with low-risk TIA or moderate to severe stroke, we recommend aspirin monotherapy (160 to 325 mg daily) (Grade 1A). For patients with high-risk TIA or minor ischemic stroke, we recommend short-term DAPT https://www.uptodate.com/contents/early-antithrombotic-treatment-of-acute-ischemic-stroke-and-transient-ischemic-attack/print 21/49 7/5/23, 12:10 PM Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack - UpToDate using aspirin and clopidogrel rather than aspirin alone (Grade 1A). Thereafter, antiplatelet treatment should continue with aspirin alone, clopidogrel alone, or aspirin- extended-release dipyridamole. (See 'Noncardioembolic etiologies' above.) However, certain additional modifications may apply: Carotid revascularization Aspirin monotherapy is preferred by some experts prior to carotid endarterectomy, while DAPT is preferred by others. DAPT is used prior to and continuing for 30 days after carotid artery stenting. (See "Carotid endarterectomy", section on 'Antiplatelet therapy' and "Overview of carotid artery stenting", section on 'Dual antiplatelet therapy'.) Intracranial large artery atherosclerosis For patients with TIA or ischemic stroke attributed to intracranial large artery atherosclerosis stenosis of 70 to 99 percent, we suggest DAPT for 90 days. (See "Intracranial large artery atherosclerosis: Treatment and prognosis", section on 'Antiplatelet therapy'.) Dissection The antithrombotic treatment of TIA or ischemic stroke caused by large artery dissection is discussed in detail separately. (See "Cerebral and cervical artery dissection: Treatment and prognosis", section on 'Choosing between antiplatelet and anticoagulation therapy'.) Long-term antiplatelet therapy Beyond the acute phase of TIA and ischemic stroke, and in the absence of an indication for oral anticoagulation, long-term antiplatelet therapy for secondary stroke prevention should be continued with aspirin alone, clopidogrel alone, or aspirin-extended-release dipyridamole. Long-term DAPT with aspirin and clopidogrel is not recommended. (See "Long-term antithrombotic therapy for the secondary prevention of ischemic stroke".) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Walter J Koroshetz, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. 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