| Unchanged | In with IS or TIA caused by extracranial carotid or vertebral artery dissection, antithrombotic therapy should be used for at least 3–6 months to prevent stroke recurrence or TIA. | I | C |
| Unchanged | For patients with IS or TIA caused by extracranial carotid or vertebral artery dissection within 3 months of onset, it is reasonable to use antiplatelet or warfarin to prevent the recurrence of stroke or TIA. | IIa | B |
| New Recommendation | For patients with IS or TIA caused by an extracranial carotid artery or vertebral artery dissection, stenting may be considered if optimal medical treatment fails. | IIb | C |
| Currently, RCTs to support the benefits of endovascular treatments in cervical artery dissection are lacking. However, some studies suggest a relatively low incidence of complications associated with endovascular treatments.194 195
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| New Recommendation | Antiplatelet drugs are recommended for patients with IS or TIA caused by intracranial arterial dissection, but the risk of bleeding should be noted. | IIb | C |
| High-quality RCTs for antithrombotic therapy for patients with intracranial artery dissection are lacking. However, a small retrospective study at a single centre suggested that anticoagulant therapy is safe in patients with intracranial artery dissection who do not have a concomitant subarachnoid haemorrhage (SAH).196 Given the risk of SAH associated with intracranial artery dissection and the lower bleeding risk of antiplatelet therapy, specifically aspirin, compared with anticoagulant therapy, it seems safer and more reasonable, based on current clinical practice and expert opinion, to administer aspirin to patients with intracranial artery dissection.197 198
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| Revised | When patients with moyamoya disease have an IS or TIA, it is recommended to effectively manage the risk factors for stroke, and perform an individualised evaluation to select the appropriate timing and method for extracranial-intracranial arterial bypass. | IIa | C |
| A meta-analysis and multicenter retrospective series have shown no difference between direct and indirect bypass surgery.199 200 An international survey conducted among renowned experts in moyamoya disease treatment reported that, compared with Asian respondents, most non-Asian respondents recommended antiplatelet therapy.201
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| New Recommendation | For patients with moyamoya disease and IS or TIA, antiplatelet therapy with aspirin is recommended to reduce the risk of stroke recurrence. When aspirin is intolerable or ineffective, clopidogrel or other thienopyridine drugs can be selected. Long-term use of antiplatelet or dual antiplatelet increases the risk of bleeding. | IIb | C |
| An international survey conducted among renowned experts in moyamoya disease treatment reported that, compared with Asian respondents, most non-Asian respondents recommended antiplatelet therapy.201 This recommendation is based on current clinical practice and expert opinion. |
| New Recommendation | For patients with autoimmune vasculitis-related stroke, apart from treatment for the autoimmune disease, antiplatelet therapy is recommended, and a multidisciplinary team should manage patients. | IIa | C |
| Currently, multiple clinical trials are focusing on evaluating the efficacy of immunotherapy in treating autoimmune vasculitis-related stroke.202–210 Based on current clinical practice and expert opinion, adding antiplatelet therapy to immunotherapy is recommended to treat autoimmune vasculitis-related stroke. It is crucial to manage this treatment with a multidisciplinary team. |
| New Recommendation | For patients with IS related to infectious vasculitis and tumour vasculitis, antiplatelet or anticoagulant therapy are both reasonable according to the patient’s condition in addition to the treatment of the primary disease. | IIa | C |
| Acyclovir is the preferred medication for the treatment of varicella-zoster virus.211 212 In patients diagnosed with neurosyphilis who present with a stroke, immediate administration of penicillin is recommended.213 Secondary stroke prevention in patients with HIV vasculopathy primarily focuses on daily antiplatelet therapy and restoring the immune system.214 215 Based on current clinical practice and expert opinion, the risk of stroke recurrence and treatment goals should be discussed with an infectious disease specialist. |
| New Recommendation | For TIA or IS patients with hyperhomocysteinemia caused by genetic diseases, it is reasonable to use vitamin B12 and folic acid to reduce blood homocysteine levels. | I | C |
| A study on the treatment of severe hyperhomocysteinemia in patients with cystathionine beta-synthase deficiency conducted in Australia, the Netherlands, and Ireland showed a significant reduction in the risk of vascular events compared with historical cohort studies (RR 0.091, 95% CI 0.043 to 0.190, p<0.001).216
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| New Recommendation | For IS or TIA patients with Fabry disease, the efficacy of enzyme replacement therapy on stroke prevention is uncertain. | IIb | B |
| An RCT in Fabry patients found that enzyme replacement therapy improved the pain-related quality of life.217 However, its impact on disease progression or mortality requires further investigation. |
| New Recommendation | Patients with carotid webs who have experienced IS or TIA, without any other identifiable causes, are recommended to receive antiplatelet therapy to prevent recurrent stroke or TIA. | I | C |
| The optimal medical treatment for symptomatic carotid webs remains unclear. Approximately 29% to 56% of patients with symptomatic carotid webs experience recurrent stroke.218 219 Carotid artery stenting or carotid endarterectomy are alternative treatment options for symptomatic carotid artery stenosis. A meta-analysis of 158 cases found that 56% of patients with medical treatment experienced recurrent stroke, while 72% of patients treated with percutaneous transluminal angioplasty did not experience recurrent stroke.219 In another prospective study, 16 patients were treated with stenting, and no recurrent strokes were reported.220
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| New Recommendation | For patients who have carotid webs and experience a recurrent stroke, despite standard medical treatment, stenting may be considered. | IIb | C |
| A meta-analysis involving 158 patients with carotid artery dissection indicated that 56% of patients treated with medication experienced recurrent strokes, while ultimately, 72% of patients underwent endovascular treatments (carotid artery stenting or carotid endarterectomy), and none of these patients experienced recurrent strokes.218 In another prospective study of 24 patients with stroke/ TIA caused by carotid artery dissection, 7 cases experienced recurrent strokes. Among them, 2 cases received dual antiplatelet therapy, 3 were on single-agent antiplatelet therapy, 1 received thrombolysis within 24 hours, and one did not receive antithrombotic treatment. In contrast, no recurrent strokes were observed among the 16 patients treated with stenting.219
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| New Recommendation | For IS or TIA patients with fibromuscular dysplasia (FMD), without any other identifiable cause, antiplatelet therapy, blood pressure control, and lifestyle management are recommended to prevent stroke recurrence. | I | C |
| In a registry study conducted in the United States, 73% of patients with FMD, received antiplatelet therapy, with aspirin being the most commonly used medication.221 222 There is no RCT comparing aspirin to placebo in patients with symptomatic or asymptomatic FMD. The recommendation to use antiplatelet therapy, blood pressure control, and lifestyle management as secondary prevention is based on current clinical practice and expert opinion. |
| New Recommendation | For IS or TIA patients with FMD, in cases where recurrent strokes persist despite the administration of standard internal medical treatment, carotid artery angioplasty may be effective in the prevention of IS. | IIb | C |
| A case series of 7 symptomatic patients with FMD showed no complications with balloon angioplasty.223 There is a lack of comparative data evaluating medical management vs endovascular treatments (such as angioplasty or stent placement) in patients with FMD and recurrent IS. Endovascular treatments are not recommended for asymptomatic FMD patients. In patients with recurrent strokes, despite optimal medical therapy, consideration may be given to endovascular treatments. The management of FMD-related arterial dissection and intracranial aneurysms follows similar principles of management as in those patient populations. |
| New Recommendation | For patients with IS or TIA caused by FMD and arterial dissection, antiplatelet therapy can be used. | IIa | C |
| In the United States fibromuscular dysplasia registry, it has been reported that 19% of patients with cervical artery dissection experience IS.224 There is a lack of high-quality studies specifically addressing the management of IS or TIA in patients with FMD complicated by arterial dissection. This recommendation is based on the expert opinion. |
| New Recommendation | For patients with vertebrobasilar dolichoectasia and a history of IS or TIA with no other identifiable causes, antiplatelet or anticoagulant therapy is reasonable for preventing recurrent strokes. | Iia | B |
| Currently, no RCTs compared antiplatelet therapy with conservative observation in the management of basilar artery dolichoectasia. However, compared with the natural history of the disease, antiplatelet therapy has been shown to reduce the risk of recurrent strokes.225 226
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| New Recommendation | For patients with isolated positive anticardiolipin antibodies but who do not meet the diagnostic criteria for antiphospholipid syndrome (APS), and present with IS or TIA, it is recommended to use antiplatelet therapy alone to reduce the risk of stroke recurrence. | I | B |
| In the subgroup analysis of the WARSS trial, individuals with a one-time positive antiphospholipid antibody did not experience a significant difference in stroke risk reduction when treated with warfarin (RR 0.99, 95% CI 0.75 to 1.13) or aspirin (RR 0.94, 95% CI 0.70 to 1.28).227
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| New Recommendation | For patients with IS or TIA who meet the diagnostic criteria for antiphospholipid syndrome, in addition to the treatment of APS, it is recommended to choose warfarin to prevent recurrent thrombotic events. | IIa | C |
| Currently, there are no specific antiplatelet trials for patients with IS or TIA who meet the diagnostic criteria for APS. The clinical expert consensus leans towards using warfarin, with a target INR of 2.0 to 3.0.228–230
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| New Recommendation | The appropriate dose of warfarin is to maintain the INR between 2.0 and 3.0 to balance the therapeutic effect and bleeding risk for patients with IS or TIA who meet the diagnostic criteria for APS. | IIa | B |
| Currently, there are no specific antiplatelet trials for patients with IS or TIA who meet the diagnostic criteria for APS. The clinical expert consensus leans towards using warfarin, with a target INR of 2.0 to 3.0.228–230
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| New Recommendation | In patients diagnosed with IS or TIA, who also present with a concomitant APS characterised by a history of thrombosis and triple positive antiphospholipid antibodies, it has been observed that the use of rivaroxaban poses a greater risk of thrombotic events compared with warfarin. Therefore, it is not recommended to use rivaroxaban as a secondary prevention of thrombotic events. | III | B |
| Multiple observational studies have shown an increased risk of arterial thrombosis and stroke recurrence with NOACs, especially in high-risk patients who are triple positive for antiphospholipid antibodies or have a history of arterial thrombosis.231–233 The ASTRO-APS trial included 48 patients with APS. After 1 year of follow-up, it was found that patients treated with apixaban had a higher incidence of stroke (6/23) compared with patients treated with warfarin (0/25). It suggests that apixaban may be less effective than warfarin for secondary stroke prevention in APS patients. However, the limited sample size and two protocol amendments in the trial limited the reliability of the conclusions drawn from this study.233
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| New Recommendation | For IS or TIA patients complicated with cancer, after evaluating the benefits and risks, antiplatelet or anticoagulant therapy should be given based on the cancer type and stage, as well as the aetiology of the vascular event. | IIb | C |
| Approximately 15% of cancer patients may experience stroke, with a high coagulable state being the most common cause of IS in cancer patients.234 The commonly used antithrombotic drugs for cancer patients with IS include low molecular weight heparin, warfarin, and NOACs. However, there is a lack of high-quality RCTs to support treatment. |
| New Recommendation | For IS or TIA patients complicated with atrial fibrillation and cancer, in addition to actively treating the primary disease, consideration may be given to using NOACs instead of warfarin to prevent stroke recurrence. | IIb | B |
| A meta-analysis, including three RCTs, a retrospective cohort study, and a case-control study, demonstrated that the use of NOACs in cancer patients with atrial fibrillation showed superior efficacy (in terms of stroke, systemic embolism, deep vein thrombosis, and all-cause mortality) and a higher level of safety (with regards to major organ bleeding) compared with warfarin.235
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