| Unchanged | For IS or TIA patients with nonvalvular atrial fibrillation, whether paroxysmal, persistent, or permanent atrial fibrillation, oral anticoagulation is recommended to reduce stroke recurrence. | I | B |
| New Recommendation | With IS or TIA combined with non-valvular atrial fibrillation, it is recommended to use warfarin or novel oral anticoagulants (NOACs) to prevent recurrent thromboembolic events. The target INR is between 2.0~3.0, if warfarin is prescribed. | I | A |
| A meta-analysis combining the data from four trials (apixaban, dabigatran, edoxaban, and rivaroxaban) found that novel oral anticoagulation therapy had a 51% reduction in haemorrhagic stroke and a 10% reduction in mortality. The incidence of IS or systemic embolism was reduced by 19%. |
| Unchanged | If anticoagulant therapy cannot be accepted for IS or TIA prevention by patients with non-valvular atrial fibrillation, aspirin alone is recommended. | I | B |
| Unchanged | For IS or TIA patients with non-valvular atrial fibrillation, if anticoagulant therapy cannot be accepted, aspirin combined with clopidogrel can also be selected, and the risk of bleeding should be assessed. | IIa | B |
| Reworded | For patients with IS or TIA combined with non-valvular atrial fibrillation, the timing of initiating anticoagulant therapy should be selected according to the severity of ischemia and the risk of haemorrhagic transformation. For patients with a high risk of ICH, anticoagulant therapy can be delayed until 14 days after onset. For patients with a low risk of ICH, anticoagulant therapy can be started within 2 to 14 days after onset to reduce the risk of stroke recurrence. Patients with TIA can initiate anticoagulant therapy after onset to reduce the risk of stroke. | IIa | C |
| New Recommendation | In patients with IS or TIA associated with non-valvular atrial fibrillation, who have contraindications to lifelong anticoagulation therapy but can tolerate anticoagulation for 45 days, the option of left atrial appendage closure may be considered to prevent stroke. | IIb | B |
| In two RCTs (PROTECT AF and PREVAIL) and a non-randomised trial (CAP), the results showed that the Watchman device did not significantly increase the risk of thrombus formation but reduced the risk of bleeding.154–157
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| New Recommendation | If patients with atrial fibrillation complicated with stroke or TIA are undergoing dialysis or have renal failure, either apixaban or warfarin can be used for stroke prevention. | IIb | B |
| A large retrospective study matched 2351 atrial fibrillation patients on dialysis taking apixaban, with 23 172 patients taking warfarin. The study found that patients taking apixaban had a 28% lower rate of bleeding events.158
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| New Recommendation | Patients with IS or TIA complicated with atrial flutter can follow the anticoagulant regimen for atrial fibrillation. | I | C |
| Previous observational studies indicated that atrial flutter incidence is lower than atrial fibrillation. However, patients with atrial flutter have an increased risk of developing atrial fibrillation, and the probability of stroke occurrence is similar to that of atrial fibrillation.159 160
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| Reworded | For IS or TIA patients with valvular atrial fibrillation (ie, moderate to severe mitral stenosis or mechanical heart valve disease with atrial fibrillation), it is rcommended to use warfarin to reduce the risk of stroke recurrence. | I | B |
| Reworded | For patients with stroke or TIA and aortic valve or nonrheumatic mitral valve disease (eg, mitral annular calcification or mitral valve prolapse) without atrial fibrillation or other indications for anticoagulation, antiplatelet therapy is recommended to reduce the risk of stroke recurrence. | I | C |
| New Recommendation | For patients with IS or TIA who have undergone bioprosthetic valve replacement and do not have atrial fibrillation or other indications for anticoagulation, it is recommended to use warfarin for 3–6 months after valve replacement, followed by long-term use of aspirin. | I | C |
| This recommendation is based on expert opinions and clinical practice. Some studies have reported an increased risk of IS in patients undergoing bioprosthetic valve replacement.161–166 Therefore, warfarin targeting an INR of 2.0–3.0 for at least 3 months postoperatively and up to 6 months is reasonable for patients undergoing bioprosthetic valve replacement and with low bleeding risk. After 3 to 6 months postoperatively, long-term treatment with daily aspirin 75–100 mg is recommended. |
| New Recommendation | For patients undergoing mechanical valve replacement, if there is a history of IS or TIA before valve replacement, and the risk of bleeding is low, it is recommended to add aspirin to warfarin. | IIa | B |
| Previous clinical studies have indicated that patients with a history of IS or TIA undergoing aortic mechanical valve replacement are at higher risk of thromboembolic complications. It is recommended to maintain the INR at a higher range (2.5–3.5) or add aspirin 75–100 mg daily.167 168
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| New Recommendation | In patients with infective endocarditis complicated by IS or TIA, it is recommended that the decision regarding early surgery should be made jointly with the patient, neurologist, and cardiologist. Early surgery may provide benefits, especially if no evidence of intracranial haemorrhage or extensive neurological injury exists. | IIb | B |
| A prospective cohort study evaluated the relationship between the timing of surgery and length of hospital stay with a 1 year mortality rate in 198 post-stroke patients, and found that early surgery was not associated with an increased risk of in-hospital mortality or a 1 year mortality rate.169
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| New Recommendation | For patients with mechanical valves with a history of stroke or TIA, anticoagulation with dabigatran is not recommended. | III | B |
| The RE-ALIGN trial compared dabigatran and warfarin to treat patients with mechanical heart valve replacement. The trial was terminated due to increased thromboembolic and bleeding events in the dabigatran group.170
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| New Recommendation | For patients with IS or TIA complicated with left ventricular thrombus, starting anticoagulant therapy with warfarin for at least 3 months (INR range 2.0–3.0) is recommended to reduce the risk of stroke recurrence. | I | B |
| In a meta-analysis of studies on thrombus after anterior myocardial infarction, vitamin K antagonists were found to reduce the incidence of stroke by 86% and achieve a left ventricular thrombus resolution rate of 68%.171
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| New Recommendation | For patients with IS or TIA with a new left ventricular thrombus (<3 months), the efficacy and safety of direct oral anticoagulant therapy to reduce the risk of stroke recurrence is uncertain. | IIb | C |
| A single-centre retrospective study showed that among 52 patients with left ventricular thrombus, 86% of patients had thrombus resolution after treatment with novel oral anticoagulants.172 However, due to the small sample size, no difference in the occurrence rate of embolic events was observed. Another large retrospective study analysed diagnosed left ventricular thrombus patients from three centres and compared 300 patients treated with warfarin to 185 patients treated with NOACs. The study found a higher incidence of stroke or systemic embolism in the group treated with novel oral anticoagulants (HR 2.71).173 174
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| New Recommendation | In patients with acute anterior wall MI and an IS or TIA with reduced left ventricular ejection fraction (EF<50%), but no evidence of left ventricular thrombus, at least 3 months of oral anticoagulant therapy may be considered to reduce cardiogenic stroke recurrence. | IIb | C |
| Patients with anterior wall MI and reduced ejection fraction are at increased risk of left ventricular thrombus formation.172 There is a lack of research on anticoagulant therapy in these patients. The recommendation for anticoagulation in this population is based on the current clinical practice and expert opinion. |
| New Recommendation | For IS or TIA patients with left ventricular assist devices, it is reasonable to use warfarin and aspirin, and anticoagulant therapy with dabigatran is not recommended. | III | C |
| Based on current clinical practice, the combination of warfarin and aspirin is the preferred approach for preventing recurrent IS in left ventricular assist device (LVAD) patients.175 The only RCT evaluating the benefits of dabigatran in LVAD implantation was terminated due to excessive thromboembolic events.176
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| Reworded | The IS of unknown etiology and PFO should undergo appropriate and comprehensive evaluation to rule out other mechanisms of stroke. If a comprehensive evaluation suggests a potential causal relationship between PFO and IS, it is recommended that treatment decisions should involve discussions on PFO closure or medical treatment between the patient, neurologists, and cardiologists. | I | C |
| New Recommendation | For IS patients aged 18 to 60 years with PFO and no other identified cause after a comprehensive evaluation, if the PFO has high-risk anatomical features such as the atrial septal aneurysm or a significant right-to-left shunt, percutaneous closure of the PFO to prevent stroke recurrence is reasonable. | IIa | B |
| Subgroup analyses of the RESPECT trial have shown significant benefits of PFO closure in patients with PFO accompanied by atrial septal aneurysm (HR 0.19, 95% CI 0.04 to 0.87, p=0.02) or substantial right-to-left shunting (HR 0.18, 95% CI 0.04 to 0.81, p=0.01).177 The results of the CLOSE trial (HR 0.03, 95% CI 0.00 to 0.26, p<0.001), the Gore REDUCE trial (HR 0.23, 95% CI 0.09 to 0.62, p=0.002), and the long-term follow-up of the RESPECT trial (HR 0.55, 95% CI 0.31 to 0.99, p=0.046) have all demonstrated significant clinical benefits of PFO closure over medical therapy in preventing stroke recurrence.177–179
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| New Recommendation | For IS patients aged 18 to 60 years with PFO and no other identified cause after a comprehensive evaluation, if the PFO does not have high-risk anatomical features such as the atrial septal aneurysm or significant right-to-left shunt, the benefit of percutaneous closure of the PFO compared with antiplatelet therapy or warfarin treatment alone is still uncertain. | IIb | C |
| The CLOSURE I, PC, and RESPECT trials did not demonstrate the superiority of PFO closure over medical therapy in unselected populations with PFO.180–182
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| New Recommendation | For patients unsuitable for transcatheter occlusion of PFO, antiplatelet drugs such as aspirin or anticoagulant drugs (including warfarin and NOACs) should be selected according to the patient’s conditions. | IIa | C |
| The current recommendation is based on clinical practice and expert opinion, as relevant trials are lacking.183
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| New Recommendation | For patients with congenital heart disease and IS or TIA, anticoagulant treatment with warfarin is reasonable. | IIa | C |
| Complex congenital heart disease is associated with an increased risk of stroke in adults.184 Based on current clinical practice and expert opinion, warfarin is considered reasonable if there are no contraindications to oral anticoagulant therapy.185
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| New Recommendation | For patients with IS or TIA who also have Fontan palliation, anticoagulant treatment with warfarin is recommended to decrease stroke recurrence. | I | C |
| The Fontan circulation and Fontan surgery could increase the risk of thromboembolic events through different pathophysiological mechanisms.186 Based on current clinical practice and expert opinion, warfarin is the preferred oral anticoagulant treatment option for patients with IS or TIA who also have Fontan palliation. |
| New Recommendation | In patients with IS or TIA, if a cardiac tumour is located on the left side, surgical resection of the tumour can help reduce the risk of stroke recurrence. | IIa | C |
| Currently, RCTs treating IS or TIA in patients with concomitant cardiac tumours are lacking.187 However, in a single-centre study, surgical resection of papillary fibroelastoma has been shown to reduce the risk of stroke. |
| New Recommendation | In patients with coronary artery or peripheral arterial diseases, the efficacy and safety of low-dose NOACs combined with antiplatelets in reducing stroke recurrence may be effective. | IIb | C |
| There are no specific study results regarding a novel antithrombotic regimen combining anticoagulation and antiplatelet therapy in the stroke population. However, the COMPASS trial found the combination of rivaroxaban 2.5 mg twice daily with aspirin 100 mg reduced stroke risk by nearly half without increasing the risk of haemorrhagic stroke in patients with coronary artery or peripheral artery disease (HR 0.51, 95% CI 0.38 to 0.68). A meta-analysis incorporating seven relevant RCTs, including patients with chronic coronary artery disease, heart failure, peripheral artery disease, and atrial fibrillation, found that low-dose novel oral anticoagulants combined with antiplatelet therapy can reduce the incidence of stroke. However, the difference was not statistically significant (IRR 0.73, 95% CI 0.53 to 1.01).188 189 The AXIOMATIC-SSP study investigated the efficacy and safety of low-dose novel oral anticoagulant combined with antiplatelet therapy to prevent recurrent stroke. The study is currently ongoing.190
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