assigned to aspirin-extended-release dipyridamole compared with clopidogrel (7.7 versus 7.9 percent), but hemorrhagic strokes were slightly increased (0.9 versus 0.5 percent). Thus, the net risk (ie, the combination of recurrent stroke plus major hemorrhage) was similar between aspirin-extended-release dipyridamole and clopidogrel (11.7 versus 11.4 percent; HR 1.03, 95% CI 0.95-1.11). New or worsening heart failure was slightly less frequent in patients assigned to aspirin- extended-release dipyridamole compared with those assigned to clopidogrel; the difference was significant (1.4 versus 1.8 percent, 95% CI 0.62-0.96). PRoFESS had a 2x2 factorial design in which the patients were also randomly assigned to telmisartan or placebo, the results of which are discussed elsewhere. (See "Antihypertensive therapy for secondary stroke prevention".) Dose Aspirin-extended-release dipyridamole, containing aspirin (25 mg) plus extended- release dipyridamole (200 mg), is given two times per day. Dipyridamole is also available as an https://www.uptodate.com/contents/long-term-antithrombotic-therapy-for-the-secondary-prevention-of-ischemic-stroke/print 11/28 7/6/23, 12:47 PM Long-term antithrombotic therapy for the secondary prevention of ischemic stroke - UpToDate immediate-release form, usually given as 50 to 100 mg three times per day, but this is seldom used alone for secondary stroke prevention. The specific dipyridamole preparation may be important. In a meta-analysis cited above, the combination of aspirin and immediate-release dipyridamole was nonsignificantly better than aspirin alone for secondary prevention of stroke (relative risk 0.83, 95% CI 0.59-1.15) [26]. By contrast, extended release dipyridamole was used in all or the vast majority of patients in the much larger ESPS-2 and ESPRIT trials [14,27], and aspirin-extended-release dipyridamole led to a greater reduction in stroke risk compared with aspirin alone [26]. Adverse effects Headache is the most common adverse effect of aspirin-extended-release dipyridamole, and one that most often leads to discontinuation of treatment. Other adverse reactions include abdominal pain, nausea, diarrhea, and vomiting. Headache was the most frequent adverse event associated with aspirin-extended-release dipyridamole in two large clinical trials, ESPS-2 and ESPRIT [14,27]. In the PRoFESS trial, discontinuation due to headache was more frequent with aspirin-extended-release dipyridamole compared with clopidogrel (5.9 versus 0.9 percent) [28]. In a study of subjects aged 55 or older treated with the combination of aspirin-extended-release dipyridamole, headache developed in 39.7 percent after a single dose, and women were significantly more likely to develop headache than men (49.6 and 28.6 percent, respectively) [29]. The headaches associated with aspirin- extended-release dipyridamole treatment were mostly self-limited, and treatment of headache with acetaminophen was not significantly better than with placebo, as measured by response at two hours (75.5 and 69.4 percent). The overall incidence of headache declined markedly over seven days to less than 20 percent. Gastric upset and/or diarrhea requiring drug cessation was also more common with dipyridamole compared with aspirin or placebo in ESPS-2. Notably, aspirin use was associated with significantly greater overall bleeding and gastrointestinal bleeding compared with dipyridamole or placebo in ESPS-2 and a subsequent meta-analysis [14,30]. In fact, in ESPS-2, the frequency of bleeding complications with dipyridamole was comparable to placebo. Concern that dipyridamole use might lead to increased rates of myocardial ischemia has been largely laid to rest by data from two large clinical trials (ESPS-2 and ESPRIT) and a meta-analysis [14,27,30,31]. This concern was related to the potential for dipyridamole to cause vasodilation of coronary vessels [32], and it first arose with the use of intravenous dipyridamole in cardiac stress testing [33]. However, accumulating data suggest that extended-release dipyridamole use for stroke prevention is not associated with an increased risk of myocardial ischemia or infarction. An analysis of data from ESPS-2 found that use of extended-release dipyridamole was not https://www.uptodate.com/contents/long-term-antithrombotic-therapy-for-the-secondary-prevention-of-ischemic-stroke/print 12/28 7/6/23, 12:47 PM Long-term antithrombotic therapy for the secondary prevention of ischemic stroke - UpToDate associated with increased cardiac ischemia or mortality in patients with a history of coronary artery disease [31], and a meta-analysis found that oral dipyridamole did not alter the rate of MI in patients with previous stroke or TIA, either when compared with control, or when administered in combination with aspirin and compared with aspirin alone [30]. In ESPRIT, the use of combination therapy with aspirin and dipyridamole, mainly extended-release dipyridamole, was associated with a nonsignificant decrease in the outcome of first cardiac event, and a significant decrease in the primary composite outcome that included death from all vascular causes and nonfatal MI [27]. Cilostazol The antiplatelet agent cilostazol is a phosphodiesterase 3 inhibitor that increases cyclic AMP and leads to reversible inhibition of platelet aggregation and arterial vasodilation. Efficacy Several randomized controlled trials and meta-analyses have found that cilostazol is effective for preventing cerebral infarction [34-36]. In the CSPS trial of over 1000 patients from Japan, cilostazol (100 mg twice daily) compared with placebo reduced the risk of stroke (relative risk reduction [RRR] 42 percent, 95% CI 9.2-62.5 percent) [34]. The CSPS II trial randomly assigned 2757 patients in Japan with a recent noncardioembolic cerebral infarction to cilostazol (100 mg twice daily) or aspirin (81 mg daily) [35]. At a mean follow-up of 29 months, the yearly rates of recurrent stroke (infarction or hemorrhage) for cilostazol and aspirin were 2.7 and 3.7 percent (HR 0.74, 95% CI 0.56-0.98), confirming that cilostazol is noninferior to aspirin for stroke prevention. Annual rates of intracranial hemorrhage or other hemorrhage requiring hospitalization were lower with cilostazol than with aspirin (0.8 versus 1.8 percent, HR 0.46, 95% CI 0.30-0.71). In the CASISP trial from China of 720 patients with recent ischemic stroke, the composite endpoint (any stroke, ischemic or hemorrhagic) at 12 to 18 months of follow-up was lower in the cilostazol group compared with the aspirin group (3.3 versus 5.6 percent), but this result was not statistically significant (HR 0.62, 95% CI 0.30-1.26) [37]. These data support the safety and efficacy of cilostazol for secondary stroke prevention in East Asian populations. However, there are as yet no high-quality data regarding the use of cilostazol for secondary stroke prevention in non-East Asian ethnic groups. Also, the twice daily dosing, lower tolerability, and higher cost of cilostazol compared with aspirin may limit its more widespread use for stroke prevention. Dosing The dose of cilostazol is 100 mg twice daily. Adverse effects In the CSPS II trial of cilostazol versus aspirin, headache, diarrhea, palpitation, dizziness, and tachycardia were more frequent with cilostazol, and more patients https://www.uptodate.com/contents/long-term-antithrombotic-therapy-for-the-secondary-prevention-of-ischemic-stroke/print 13/28 7/6/23, 12:47 PM Long-term antithrombotic therapy for the secondary prevention of ischemic stroke - UpToDate discontinued cilostazol than aspirin (20 versus 12 percent) [35]. Other potential adverse reactions include diarrhea, infection, and rhinitis. Others Ticlopidine Ticlopidine is a thienopyridine with a chemical structure and mechanism of action similar to clopidogrel. Despite the evidence of benefit in randomized trials, ticlopidine is not considered a first-line antiplatelet agent for stroke prevention because of the risk of severe neutropenia and relatively high cost. Efficacy The CATS trial enrolled over 1000 patients between one week and four months after ischemic stroke [38]. At a mean of 24 months, the primary composite end point of stroke, MI, and vascular death was lower with ticlopidine compared with placebo (10.8 versus 15.3 percent, RRR 30 percent). The benefit was smaller by intention-to-treat analysis (RRR 23 percent). The TASS trial compared ticlopidine (500 mg/d) with aspirin (1300 mg/d) in 3069 patients with a recent TIA or mild stroke [39]. At three-year follow-up, ticlopidine reduced the primary end point (nonfatal stroke or death) compared with aspirin (17 versus 19 percent). Ticlopidine also reduced the rate of fatal and nonfatal stroke compared with aspirin (10 versus 13 percent, respectively, RRR 21 percent, 95% CI 4-38). The AAASPS trial compared ticlopidine (500 mg/day) with aspirin (650 mg/day) in 1809 Black patients with noncardioembolic ischemic stroke [40]. At two-year follow-up, there was no significant difference in the primary end point (stroke, MI, vascular death) between ticlopidine and aspirin. Dose The dose of ticlopidine is 250 mg twice daily. The drug is no longer available in the United States. Adverse effects The most serious complication of ticlopidine therapy is severe neutropenia, which occurs in approximately 1 percent of patients. Thus, patients must have a complete blood count with differential prior to treatment initiation and then weekly for the first three months of therapy; more frequent monitoring is recommended for patients whose absolute neutrophil counts are consistently declining or are 30 percent less than baseline. Other common side effects, which occur more frequently with ticlopidine than aspirin, are rash and diarrhea. Triflusal Triflusal is an antiplatelet agent that is structurally related to aspirin. It is available as a licensed pharmaceutical in some European and Latin American countries but is considered investigational in the United States. In a randomized trial with 2113 patients, the effectiveness of triflusal (600 mg/day) was similar to aspirin (325 mg/day) at preventing vascular events after https://www.uptodate.com/contents/long-term-antithrombotic-therapy-for-the-secondary-prevention-of-ischemic-stroke/print 14/28 7/6/23, 12:47 PM Long-term antithrombotic therapy for the secondary prevention of ischemic stroke - UpToDate stroke, but it did have a lower rate of hemorrhagic complications [41]. Similar findings were noted in a smaller randomized trial and a meta-analysis of four trials [42,43]. It is not clear whether triflusal would have had a lower rate of hemorrhagic complications than lower-dose aspirin [44]. Dual antiplatelet therapy The short-term use of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is beneficial compared with aspirin alone in some patients with acute ischemic stroke syndromes ( algorithm 1 and algorithm 2), as reviewed elsewhere. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack".) However, evidence from randomized trials suggests that long-term DAPT has no such benefit for stroke risk reduction, but rather appears to be harmful due to an increased risk of bleeding. Aspirin plus clopidogrel For the vast majority of patients with ischemic stroke, the long- term use of DAPT with aspirin and clopidogrel does not offer greater benefit for stroke prevention than either agent alone but does substantially increase the risk of bleeding complications [45-49]. The MATCH trial enrolled 7599 patients with stroke or TIA who also had some additional "high-risk" feature, defined as prior MI, prior stroke (in addition to the index event), diabetes, angina, or symptomatic peripheral artery disease [45]. Patients were randomly assigned to the combination of clopidogrel (75 mg daily) plus aspirin (75 mg daily) or clopidogrel (75 mg daily) alone. Follow-up was 18 months. Compared with clopidogrel alone, aspirin plus clopidogrel treatment did not reduce the risk of major vascular events (relative risk reduction 6.4 percent, 95% CI -4.6 to 16.3 percent) but did result in more life- threatening bleeding complications, mainly intracranial and gastrointestinal. Over the 18- month trial period, there was an absolute excess of 1.3 percent for life-threatening hemorrhage (95% CI 0.6-1.9) and an additional 1.3 percent for major hemorrhage in patients assigned combination therapy. Overall, treatment with aspirin and clopidogrel compared with clopidogrel alone might prevent 10 ischemic events per 1000 at the cost of 13 life-threatening hemorrhages per 1000 treated. There are several limitations of MATCH. For instance, 54 percent of MATCH subjects qualified for trial entry because of a lacunar stroke, a stroke subtype that has the lowest recurrence risk [50]. Furthermore, data regarding interaction between treatment and stroke mechanism were not reported, raising the question of whether combination therapy might still play a role in particular stroke subtypes. The CHARISMA trial evaluated aspirin plus clopidogrel versus aspirin alone in 15,603 patients with either documented cardiovascular disease (coronary, ischemic https://www.uptodate.com/contents/long-term-antithrombotic-therapy-for-the-secondary-prevention-of-ischemic-stroke/print 15/28 7/6/23, 12:47 PM Long-term antithrombotic therapy for the secondary prevention of ischemic stroke - UpToDate cerebrovascular, or peripheral arterial) or, in 21 percent of patients, multiple atherothrombotic risk factors (eg, diabetes, hypertension, primary hypercholesterolemia, current smoking, asymptomatic carotid stenosis 70 percent) [46]. Patients were randomly assigned to low-dose aspirin (75 to 162 mg/day) plus either clopidogrel (75 mg/day) or placebo. At a median follow-up of 28 months, combined aspirin plus clopidogrel treatment did not reduce the risk of the composite end point (MI, stroke of any cause, or death from cardiovascular causes) compared with aspirin alone (6.8 versus 7.3 percent, relative risk 0.93, 95% CI 0.83-1.05), but did increase in moderate bleeding (2.1 versus 1.3 percent) and severe bleeding (1.7 versus 1.3 percent), although the latter did not reach statistical significance. The SPS3 trial evaluated over 3000 patients with subcortical (ie, lacunar) stroke confirmed by magnetic resonance imaging (MRI) [51]. The arm testing the combination of aspirin plus clopidogrel versus aspirin alone was terminated before completion because of a higher frequency of bleeding events (mostly systemic) and a higher mortality rate in patients assigned to DAPT compared with those assigned to aspirin only. In the final analysis, subjects treated with aspirin plus clopidogrel compared with aspirin alone had a significantly increased annual rate of both major hemorrhage (2.1 versus 1.1 percent, HR 1.97, 95% CI 1.41-2.71) and all-cause mortality (2.1 versus 1.4 percent, HR 1.52, 95% CI 1.14- 2.04) [49]. Furthermore, treatment with aspirin and clopidogrel compared with aspirin alone in did not reduce the risk of recurrent stroke [49]. Cilostazol plus aspirin or clopidogrel The potential utility of DAPT using cilostazol was explored in the open-label CSPS.com trial in Japan, which enrolled 1884 adult patients with noncardioembolic ischemic stroke who had 50 percent stenosis of a major intracranial or extracranial artery, or two or more vascular risk factors [52]. The patients were assigned in a 1:1 ratio to antiplatelet monotherapy using either aspirin or clopidogrel, or to DAPT using cilostazol combined with either aspirin or clopidogrel [52]. During a median follow-up of 1.4 years, the rate of recurrent ischemic stroke was lower for the DAPT group compared with the monotherapy group (3 versus 7 percent, HR 0.49, 95% CI 0.31-0.76). The rates of serious adverse events and bleeding events were similar between the groups. Limitations to this trial include early stopping before reaching the planned 4000 enrollment due to slow recruitment, resulting in a lower number of event rates, the varying combinations of antiplatelet medications and dosages of aspirin, and the unblinded treatment. Combination antiplatelet and anticoagulant therapy Aspirin combined with low-dose rivaroxaban (2.5 orally twice a day) is another reasonable treatment option for some patients with non-lacunar, non-cardioembolic ischemic stroke and evidence of systemic atherosclerosis. https://www.uptodate.com/contents/long-term-antithrombotic-therapy-for-the-secondary-prevention-of-ischemic-stroke/print 16/28 7/6/23, 12:47 PM Long-term antithrombotic therapy for the secondary prevention of ischemic stroke - UpToDate This approach is based primarily on the results of the COMPASS trial, which randomly assigned over 27,000 patients with stable coronary artery disease or peripheral arterial disease to one of three treatment arms: one, rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily; two, rivaroxaban 5 mg twice daily; or three, aspirin 100 mg daily [53]. Patients with a history of lacunar stroke or with cardioembolic stroke requiring anticoagulation were excluded from enrollment. The mean follow-up was 23 months. Compared with those assigned to aspirin alone, patients assigned to rivaroxaban plus aspirin had a decrease in the annualized composite outcome of cardiovascular mortality, stroke, or myocardial infarction (4.1 versus 5.4 percent, absolute risk reduction [ARR] 1.3 percent, HR 0.76, 95% CI 0.66 to 0.86) and a decrease in ischemic stroke (0.7 versus 1.4 percent, ARR 0.7 percent, HR 0.51, 95% CI 0.38-0.68). Similarly, in the subgroup of 1032 patients with prior stroke, aspirin and rivaroxaban decreased the composite rate of cardiovascular death, stroke, or myocardial infarction (3.7 percent, versus 6.5 percent with aspirin alone, ARR 2.8 percent, HR 0.57, 95% CI 0.34-0.96) [54]; thus, the ARR for patients with prior stroke was more than double that observed for the overall trial cohort. As expected, those assigned to combination therapy in COMPASS had an increase in major bleeding events (3.1 versus 1.9 percent, absolute risk increase 1.2 percent, HR 1.70, 95% CI 1.40- 2.05), with the gastrointestinal tract being the most common site of major bleeding [53]. However, there was no difference between the two groups in fatal bleeding (0.2 versus 0.1 percent) or intracranial bleeding (0.2 percent in both arms). Similar findings for risk reduction of ischemic stroke were reported in the COMMANDER-HF trial, which randomly assigned over 5000 patients with chronic heart failure, left ventricular ejection fraction 40 percent, coronary artery disease, elevated plasma natriuretic peptide level, and no atrial fibrillation to receive rivaroxaban 2.5 mg twice daily or placebo [55]. At baseline, approximately 93 percent of the patients were on aspirin (alone or in combination with a thienopyridine), and approximately 35 percent were taking DAPT. During a median follow-up of 21 months, there was no significant difference in all-cause mortality between the rivaroxaban and placebo groups, but the risk of stroke was reduced in the group assigned to rivaroxaban (2 versus 3 percent, ARR 1 percent, HR 0.66, 95% CI 0.47-0.95). The risk of major bleeding was higher in the rivaroxaban group (3.3 versus 2.0 percent), but there was no significant difference between groups for fatal bleeding (0.4 percent in both groups) or for bleeding into a critical space (0.5 versus 0.8 percent). SOCIETY GUIDELINE LINKS 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".) https://www.uptodate.com/contents/long-term-antithrombotic-therapy-for-the-secondary-prevention-of-ischemic-stroke/print 17/28 7/6/23, 12:47 PM Long-term antithrombotic therapy for the secondary prevention of ischemic stroke - UpToDate 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)" and "Patient education: Medicines after an ischemic stroke (The Basics)") Beyond the Basics topics (see "Patient education: Stroke symptoms and diagnosis (Beyond the Basics)" and "Patient education: Transient ischemic attack (Beyond the Basics)" and "Patient education: Ischemic stroke treatment (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Acute antiplatelet therapy The use of antiplatelet therapy in the acute period of ischemic stroke and transient ischemic attack (TIA), including the short-term use of dual antiplatelet therapy (DAPT), is discussed in detail elsewhere ( algorithm 1 and algorithm 2). (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack".) Options for long-term antiplatelet therapy Aspirin, clopidogrel, and the combination of aspirin-extended-release dipyridamole are all acceptable options for preventing recurrent noncardioembolic ischemic stroke. Cilostazol is a reasonable option for patients of East Asian ethnicity, and for all patients if the other agents are not available or tolerated. (See 'Aspirin' above and 'Clopidogrel' above and 'Aspirin plus dipyridamole' above.) Our recommendations For secondary prevention of stroke in patients with a history of noncardioembolic stroke or TIA of atherothrombotic, lacunar (small vessel occlusive type), or cryptogenic type, we recommend treatment with an antiplatelet agent using either https://www.uptodate.com/contents/long-term-antithrombotic-therapy-for-the-secondary-prevention-of-ischemic-stroke/print 18/28 7/6/23, 12:47 PM Long-term antithrombotic therapy for the secondary prevention of ischemic stroke - UpToDate aspirin, clopidogrel, or aspirin-extended-release dipyridamole (Grade 1A). We suggest antiplatelet therapy using either clopidogrel (75 mg daily) as monotherapy or the combination of aspirin-extended-release dipyridamole (25 mg/200 mg twice a day), rather than aspirin alone (Grade 2B). The choice between clopidogrel and aspirin-extended- release dipyridamole is dependent mainly on patient tolerance and contraindications. Aspirin is appropriate for patients who cannot afford or tolerate clopidogrel or aspirin- extended-release dipyridamole. (See 'Aspirin' above and 'Clopidogrel' above and 'Aspirin plus dipyridamole' above.) Aspirin dose Although the optimal dose of aspirin is uncertain, there is no compelling evidence that any specific dose is more effective than another, and fewer gastrointestinal side effects and bleeding occur with lower doses ( 325 mg a day). We recommend a dose of 50 to 100 mg daily when using aspirin for the secondary prevention of ischemic stroke (Grade 1B). (See 'Dose of aspirin' above.) Limited role for long-term dual antiplatelet therapy For most patients with a noncardioembolic stroke or TIA, we recommend not using aspirin and clopidogrel in combination for long-term stroke prevention, given the lack of greater efficacy compared with clopidogrel alone and the substantially increased risk of bleeding complications (Grade 1A). (See 'Aspirin plus clopidogrel' above.) Possible exceptions include patients with concurrent indications for dual antiplatelet therapy (eg, selected patients with a recent acute myocardial infarction, other acute coronary syndrome, or arterial stent placement including carotid stenting); these are discussed elsewhere. (See "Acute ST-elevation myocardial infarction: Antiplatelet therapy" and "Acute non-ST-elevation acute coronary syndromes: Early antiplatelet therapy" and "Antithrombotic therapy for elective percutaneous coronary intervention: General use" and "Long-term antiplatelet therapy after coronary artery stenting in stable patients" and "Overview of carotid artery stenting".) Role of combined antiplatelet and anticoagulant therapy For high-risk patients with noncardioembolic, nonlacunar stroke and evidence of peripheral, coronary, or cerebrovascular atherosclerosis, aspirin combined with low-dose rivaroxaban (2.5 orally twice a day) is a reasonable treatment option. (See 'Combination antiplatelet and anticoagulant therapy' above.) Atrial fibrillation Prevention of recurrent cardioembolic stroke in patients with atrial fibrillation is discussed separately. (See "Atrial fibrillation in adults: Use of oral anticoagulants".) https://www.uptodate.com/contents/long-term-antithrombotic-therapy-for-the-secondary-prevention-of-ischemic-stroke/print 19/28 7/6/23, 12:47 PM Long-term antithrombotic therapy for the secondary prevention of ischemic stroke - UpToDate Use of UpToDate is subject to the Terms of Use. REFERENCES 1. 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. 2. 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Topic 1086 Version 56.0 https://www.uptodate.com/contents/long-term-antithrombotic-therapy-for-the-secondary-prevention-of-ischemic-stroke/print 23/28 7/6/23, 12:47 PM Long-term antithrombotic therapy for the secondary prevention of ischemic stroke - UpToDate GRAPHICS Antithrombotic therapy according to cause of transient ischemic attack (TIA) This algorithm is intended to provide basic guidance regarding the use of antithrombotic therapy based on mechanism for patients with a TIA. For further details, including suggested dosing regimens of antithrombot agents, refer to the relevant UpToDate topic reviews. ICA: internal carotid artery; CEA: carotid endarterectomy; CAS: carotid artery stenting; DAPT: dual antiplatelet 2 therapy (eg, aspirin and clopidogrel, or aspirin and ticagrelor); ABCD : age, blood pressure, clinical features, duration of symptoms, and diabetes; BP: blood pressure; SBP: systolic blood pressure; DBP: diastolic blood pressure. Indications for long-term oral anticoagulation include atrial fibrillation, ventricular thrombus, mechanical h valve, and treatment of venous thromboembolism. Some experts prefer DAPT based upon observational evidence. Long-term single-agent antiplatelet therapy using aspirin, clopidogrel, or aspirin-extended-release dipyrida https://www.uptodate.com/contents/long-term-antithrombotic-therapy-for-the-secondary-prevention-of-ischemic-stroke/print 24/28 7/6/23, 12:47 PM Long-term antithrombotic therapy for the secondary prevention of ischemic stroke - UpToDate Graphic 131695 Version 3.0 https://www.uptodate.com/contents/long-term-antithrombotic-therapy-for-the-secondary-prevention-of-ischemic-stroke/print 25/28 7/6/23, 12:47 PM Long-term antithrombotic therapy for the secondary prevention of ischemic stroke - 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/long-term-antithrombotic-therapy-for-the-secondary-prevention-of-ischemic-stroke/print 26/28 7/6/23, 12:47 PM Long-term antithrombotic therapy for the secondary prevention of ischemic stroke - 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.