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*For medical professionals' reference only, Professor Xia Jian from the Department of Neurology, Xiangya Hospital of Central South University made a wonderful interpretation of these hot issues
.
In patients with ischemic stroke and atrial fibrillation, the timing and treatment strategy of anticoagulation have been perplexing us.
The 24th National Neurology Conference of the Chinese Medical Association taught us about ischemic stroke and atrial fibrillation anticoagulation.
Opportunity for treatment——Professor Xia Jian from the Department of Neurology, Xiangya Hospital of Central South University gave a wonderful report on this hot topic
.
Studies have shown that among 14 natural populations (age ≥ 30 years old) in 13 provinces in China, the risk of stroke in patients with atrial fibrillation is 6 times that of non-AF patients, the 1-year disability rate has nearly doubled, and the 1-year mortality rate has increased.
Nearly 3 times higher, the risk of stroke recurrence within a year of patients is 5.
7 times that of non-AF patients
.
However, the mechanism of stroke caused by atrial fibrillation has not yet been fully clarified.
It is now believed that left atrial appendage thrombosis is the main source of embolism caused by atrial fibrillation
.
Therefore, the comprehensive management of patients with atrial fibrillation is essential to improve the prognosis
.
Today's lecture is mainly based on the anticoagulation treatment of patients with ischemic stroke and atrial fibrillation
.
01How to choose anticoagulant drugs for ischemic stroke complicated with atrial fibrillation? The benefits of anticoagulation in atrial fibrillation are mainly due to the reduction in the risk of stroke
.
There are currently two anticoagulant drugs available for selection: warfarin and new oral anticoagulants (NOAC), the latter including apixaban, rivaroxaban, edoxaban and so on
.
As a traditional warfarin anticoagulation therapy, the following limitations: a narrow therapeutic window, unpredictable anticoagulant effect, require frequent monitoring, slow onset, drug and food interactions
.
NOAC is a new type of anticoagulant with the following advantages: a wider therapeutic window, predictable anticoagulant effect, no need for routine monitoring, and no food-drug interaction
.
Currently, warfarin is the standard treatment for valvular atrial fibrillation
.
Consider that warfarin has become the standard treatment in valvular atrial fibrillation, rheumatic mitral stenosis, mechanical valve replacement, 3 months after bioprosthetic valve replacement, or 3 months after mitral valve repair with atrial fibrillation There is no evidence to support the use of NOAC for antithrombotic therapy, so warfarin should be used
.
Among the high-level recommendations of the latest domestic and foreign guidelines, NOAC has more advantages in anticoagulation for ischemic stroke/transient ischemic attack (TIA) combined with non-valvular atrial fibrillation
.
A number of studies have also confirmed the effectiveness and safety of NOAC
.
The following are major recommendations: 2021 American Heart Association (AHA)/American Stroke Association (ASA) recommendation: For patients with ischemic stroke or TIA combined with non-valvular atrial fibrillation, if there is no moderate to severe mitral stenosis or mechanical For valves, NOAC (apixaban, dabigatran, edoxaban, rivaroxaban) is recommended to be superior to warfarin to reduce stroke recurrence
.
2020 European Society of Cardiology (ESC)/European Society of Cardiothoracic Surgery (EACTS) recommends that patients at risk of atrial fibrillation and stroke need to receive anticoagulant therapy to prevent stroke.
In patients who meet the NOAC indications, NOAC is better than vitamin K Antagonist (I/A)
.
2019 AHA/European Society of Cardiology (ACC)/American Heart Rhythm Society (HRS) recommendation: In patients with atrial fibrillation used by NOAC (except for patients with moderate to severe mitral stenosis or mechanical valve), NOAC is recommended as the first choice, and vitamin K antagonism is the second choice Agent (I/A)
.
2018 Chinese Medical Association recommendation: In the choice of anticoagulant drugs, if there is no contraindication to NOAC, NOAC (I/A) can be the first choice
.
Attachment: The first step of the "3-step" process of anticoagulation for atrial fibrillation combined with stroke is to identify patients at risk of stroke
.
The second step is to identify correctable bleeding risk factors and calculate the HAS-BLED score
.
The third step is to start NOAC or vitamin K antagonist
.
02When is the anticoagulant therapy for ischemic stroke combined with atrial fibrillation started? The RAF study comprehensively explored the timing of anticoagulation therapy, and the results suggest that starting anticoagulation therapy on days 4-14 after stroke reduces the primary endpoint event, which is significantly better than the treatment 4 days before and after 14 days
.
The RAF-NOAC study shows that it is safe to start NOAC treatment within 3-14 days
.
The VISTA study showed that early anticoagulation (2-3 days after stroke) has a lower risk of recurrent ischemic stroke than delayed anticoagulation (>3 days)
.
Figure 1: The 2021 AHA/ASA Guidelines (Tuyuan Professor Xia Jian's PPT) When to start anticoagulation in patients with atrial fibrillation, the latest 2021 AHA/ASA Guidelines recommend: ①For TIA patients with non-valvular atrial fibrillation, start anticoagulation immediately Treatment to reduce the risk of stroke recurrence is reasonable
.
②For most stroke patients with atrial fibrillation and low risk of hemorrhage transformation, it is reasonable to start anticoagulation therapy 2-14 days after the onset to reduce the risk of stroke recurrence
.
③For stroke patients with a high risk of cerebral infarction hemorrhage conversion, anticoagulation therapy can be delayed until 14 days after the onset of the disease to reduce the risk of cerebral hemorrhage
.
03Can the thrombolysis of ischemic stroke in patients with atrial fibrillation during oral anticoagulation? For patients who use warfarin before the onset of stroke, the INR value needs to be monitored for thrombolysis.
GWTG-stroke study recommendation: intravenous thrombolysis is recommended for patients who have used vitamin K antagonists before acute stroke but the onset time is within 4.
5 hours and the INR ≤ 1.
7
.
For patients who use NOAC before the onset of stroke, the coagulation function should be monitored for thrombolysis.
The 2021 European Stroke Organization (ESO) Acute Ischemic Stroke Intravenous Thrombolysis Guidelines recommend: ① Use NOAC within 48 hours of stroke onset, anti-Xa activity <0.
5U/ In patients with mL or thrombin time <60s, intravenous alteplase is recommended for thrombolysis; ②If dabigatran is used within 48 hours before the onset of stroke, it is recommended to use edacizumab and alteplase intravenously Bolt
.
Stroke occurred during oral anticoagulant drug "2021 ESO Acute Ischemic Stroke Intravenous Thrombolysis Guidelines" recommended that thrombolysis should not be recommended in the following situations: ①Patients using vitamin K antagonists before stroke: Even if the onset time is <4.
5 h, the international normalized ratio When (INR)>1.
7 or the thrombin test is unknown, thrombolysis is not recommended
.
②Patients using NOAC 48 hours before stroke: Even if the onset time is less than 4.
5 hours, there is no specific coagulation test result (anti-Xa activity of factor Xa inhibitor, thrombin time of dabigatran or NOAC blood concentration).
Thrombolysis is recommended
.
04When should anticoagulation be restarted after bleeding? Need to dynamically identify the risk of bleeding during anticoagulation: correctable risk factors: high blood pressure (systolic blood pressure> 160mmHg), unstable INR when taking vitamin K antagonists, or time for INR to reach the therapeutic target range value <60%, combined application increase Hemorrhage-prone drugs such as anti-platelet drugs and non-steroidal anti-inflammatory drugs, alcohol addiction (≥8 alcohol consumption/week)
.
Potentially correctable risk factors: anemia, impaired renal function (serum creatinine>200μmol/L), impaired liver function, decreased platelet count or function
.
Biomarkers of bleeding risk: high-sensitivity troponin, growth differentiation factor-15, serum creatinine/estimated creatinine clearance
.
Uncorrectable risk factors: age (greater than 65 years old), major bleeding, previous stroke, nephropathy requiring dialysis treatment, liver cirrhosis, malignant diseases, genetic factors
.
Treatment of vitamin K antagonist-related bleeding: mild bleeding: delay vitamin K antagonist until INR<2
.
Moderate to severe bleeding: need fluid replacement, correct the cause of bleeding, add vitamin K1
.
Severe: Need to combine prothrombin complex, fresh frozen plasma
.
The timing of restarting anticoagulation after bleeding is 4 weeks later
.
If the risk of atrial fibrillation embolism is high, and the cause of bleeding and related risk factors can be corrected, and the risk of new intracranial hemorrhage is low, anticoagulation can be started after 4 to 8 weeks; if the patient has both a high risk of bleeding and a risk of ischemia High, the left atrial appendage closure surgery can be performed on the patient to replace anticoagulation therapy
.
05How to treat ischemic stroke + atrial fibrillation + severe atherosclerosis? ①Stroke patients have both atrial fibrillation and atherosclerosis: anticoagulation or antiplaten? The 2019 AHA/ASA Guidelines for the Management of Patients with Acute Ischemic Stroke recommends: For patients with a history of ischemic stroke, atrial fibrillation, and coronary heart disease, add antiplatelet therapy to oral anticoagulants to reduce ischemia The benefit of the risk of sexual cardiovascular and cerebrovascular events is unclear
.
Indications for anticoagulation of atrial fibrillation: Both CHADS2 score and CHADS2-VASC score stipulate that as long as there is cerebral infarction/TIA, the score should be at least 2 points, and anticoagulation therapy is required
.
Anticoagulation is preferred, and antiplatelet drugs are not necessarily added at the same time
.
②Antithrombotic treatment after atrial fibrillation combined with percutaneous coronary intervention (PCI): double or triple? It is recommended that anticoagulation therapy be preferred, and antiplatelet therapy drugs may not be added at the same time, because it may increase the risk of bleeding
.
Consensus recommendations for antithrombotic therapy in patients with APSC atrial fibrillation in 2021: (1) Atrial fibrillation + elective PCI: direct oral anticoagulant (DOAC) + aspirin + clopidogrel triple antithrombotic for 1 month DOAC + clopidogrel double antithrombotic Long-term maintenance of DOAC single-agent anticoagulation for 6 months (2) Atrial fibrillation + acute coronary syndrome (ACS) (receiving PC): DOAC + aspirin + P2Y12 inhibitor triple antithrombotic to 1 month DOAC + P2Y12 inhibitor dual anticoagulant Long-term maintenance of DOAC single-agent anticoagulation for 12 months (3) Atrial fibrillation + ACS (drug therapy) DOAC+P2Y12 inhibitor dual antithrombotic to 12 months DOAC single-agent anticoagulation and long-term maintenance of stroke risk control for anticoagulation therapy When the rate is low, other treatment options: ATTEST study: radiofrequency ablation can reduce the risk of atrial fibrillation progression by 90%
.
In theory, sealing the left atrial appendage is one of the effective ways to prevent embolic complications in patients with atrial fibrillation
.
Summary: There are two main drug options for anticoagulation therapy in patients with ischemic stroke and atrial fibrillation: warfarin and NOAC.
The anticoagulation options for non-valvular atrial fibrillation and valvular atrial fibrillation are different, and anticoagulation is initiated after stroke.
The best time is 2-14 days after the onset of the disease.
When the anticoagulation treatment encounters bleeding, requires thrombolysis, antiplatelet therapy, etc.
, it is necessary to comprehensively evaluate the benefits and risks of the patient, and choose a reasonable treatment plan
.
For patients with ischemic stroke and atrial fibrillation, if the stroke risk control rate of anticoagulation therapy is low, radiofrequency ablation and left atrial appendage occlusion can also be considered
.
.
In patients with ischemic stroke and atrial fibrillation, the timing and treatment strategy of anticoagulation have been perplexing us.
The 24th National Neurology Conference of the Chinese Medical Association taught us about ischemic stroke and atrial fibrillation anticoagulation.
Opportunity for treatment——Professor Xia Jian from the Department of Neurology, Xiangya Hospital of Central South University gave a wonderful report on this hot topic
.
Studies have shown that among 14 natural populations (age ≥ 30 years old) in 13 provinces in China, the risk of stroke in patients with atrial fibrillation is 6 times that of non-AF patients, the 1-year disability rate has nearly doubled, and the 1-year mortality rate has increased.
Nearly 3 times higher, the risk of stroke recurrence within a year of patients is 5.
7 times that of non-AF patients
.
However, the mechanism of stroke caused by atrial fibrillation has not yet been fully clarified.
It is now believed that left atrial appendage thrombosis is the main source of embolism caused by atrial fibrillation
.
Therefore, the comprehensive management of patients with atrial fibrillation is essential to improve the prognosis
.
Today's lecture is mainly based on the anticoagulation treatment of patients with ischemic stroke and atrial fibrillation
.
01How to choose anticoagulant drugs for ischemic stroke complicated with atrial fibrillation? The benefits of anticoagulation in atrial fibrillation are mainly due to the reduction in the risk of stroke
.
There are currently two anticoagulant drugs available for selection: warfarin and new oral anticoagulants (NOAC), the latter including apixaban, rivaroxaban, edoxaban and so on
.
As a traditional warfarin anticoagulation therapy, the following limitations: a narrow therapeutic window, unpredictable anticoagulant effect, require frequent monitoring, slow onset, drug and food interactions
.
NOAC is a new type of anticoagulant with the following advantages: a wider therapeutic window, predictable anticoagulant effect, no need for routine monitoring, and no food-drug interaction
.
Currently, warfarin is the standard treatment for valvular atrial fibrillation
.
Consider that warfarin has become the standard treatment in valvular atrial fibrillation, rheumatic mitral stenosis, mechanical valve replacement, 3 months after bioprosthetic valve replacement, or 3 months after mitral valve repair with atrial fibrillation There is no evidence to support the use of NOAC for antithrombotic therapy, so warfarin should be used
.
Among the high-level recommendations of the latest domestic and foreign guidelines, NOAC has more advantages in anticoagulation for ischemic stroke/transient ischemic attack (TIA) combined with non-valvular atrial fibrillation
.
A number of studies have also confirmed the effectiveness and safety of NOAC
.
The following are major recommendations: 2021 American Heart Association (AHA)/American Stroke Association (ASA) recommendation: For patients with ischemic stroke or TIA combined with non-valvular atrial fibrillation, if there is no moderate to severe mitral stenosis or mechanical For valves, NOAC (apixaban, dabigatran, edoxaban, rivaroxaban) is recommended to be superior to warfarin to reduce stroke recurrence
.
2020 European Society of Cardiology (ESC)/European Society of Cardiothoracic Surgery (EACTS) recommends that patients at risk of atrial fibrillation and stroke need to receive anticoagulant therapy to prevent stroke.
In patients who meet the NOAC indications, NOAC is better than vitamin K Antagonist (I/A)
.
2019 AHA/European Society of Cardiology (ACC)/American Heart Rhythm Society (HRS) recommendation: In patients with atrial fibrillation used by NOAC (except for patients with moderate to severe mitral stenosis or mechanical valve), NOAC is recommended as the first choice, and vitamin K antagonism is the second choice Agent (I/A)
.
2018 Chinese Medical Association recommendation: In the choice of anticoagulant drugs, if there is no contraindication to NOAC, NOAC (I/A) can be the first choice
.
Attachment: The first step of the "3-step" process of anticoagulation for atrial fibrillation combined with stroke is to identify patients at risk of stroke
.
The second step is to identify correctable bleeding risk factors and calculate the HAS-BLED score
.
The third step is to start NOAC or vitamin K antagonist
.
02When is the anticoagulant therapy for ischemic stroke combined with atrial fibrillation started? The RAF study comprehensively explored the timing of anticoagulation therapy, and the results suggest that starting anticoagulation therapy on days 4-14 after stroke reduces the primary endpoint event, which is significantly better than the treatment 4 days before and after 14 days
.
The RAF-NOAC study shows that it is safe to start NOAC treatment within 3-14 days
.
The VISTA study showed that early anticoagulation (2-3 days after stroke) has a lower risk of recurrent ischemic stroke than delayed anticoagulation (>3 days)
.
Figure 1: The 2021 AHA/ASA Guidelines (Tuyuan Professor Xia Jian's PPT) When to start anticoagulation in patients with atrial fibrillation, the latest 2021 AHA/ASA Guidelines recommend: ①For TIA patients with non-valvular atrial fibrillation, start anticoagulation immediately Treatment to reduce the risk of stroke recurrence is reasonable
.
②For most stroke patients with atrial fibrillation and low risk of hemorrhage transformation, it is reasonable to start anticoagulation therapy 2-14 days after the onset to reduce the risk of stroke recurrence
.
③For stroke patients with a high risk of cerebral infarction hemorrhage conversion, anticoagulation therapy can be delayed until 14 days after the onset of the disease to reduce the risk of cerebral hemorrhage
.
03Can the thrombolysis of ischemic stroke in patients with atrial fibrillation during oral anticoagulation? For patients who use warfarin before the onset of stroke, the INR value needs to be monitored for thrombolysis.
GWTG-stroke study recommendation: intravenous thrombolysis is recommended for patients who have used vitamin K antagonists before acute stroke but the onset time is within 4.
5 hours and the INR ≤ 1.
7
.
For patients who use NOAC before the onset of stroke, the coagulation function should be monitored for thrombolysis.
The 2021 European Stroke Organization (ESO) Acute Ischemic Stroke Intravenous Thrombolysis Guidelines recommend: ① Use NOAC within 48 hours of stroke onset, anti-Xa activity <0.
5U/ In patients with mL or thrombin time <60s, intravenous alteplase is recommended for thrombolysis; ②If dabigatran is used within 48 hours before the onset of stroke, it is recommended to use edacizumab and alteplase intravenously Bolt
.
Stroke occurred during oral anticoagulant drug "2021 ESO Acute Ischemic Stroke Intravenous Thrombolysis Guidelines" recommended that thrombolysis should not be recommended in the following situations: ①Patients using vitamin K antagonists before stroke: Even if the onset time is <4.
5 h, the international normalized ratio When (INR)>1.
7 or the thrombin test is unknown, thrombolysis is not recommended
.
②Patients using NOAC 48 hours before stroke: Even if the onset time is less than 4.
5 hours, there is no specific coagulation test result (anti-Xa activity of factor Xa inhibitor, thrombin time of dabigatran or NOAC blood concentration).
Thrombolysis is recommended
.
04When should anticoagulation be restarted after bleeding? Need to dynamically identify the risk of bleeding during anticoagulation: correctable risk factors: high blood pressure (systolic blood pressure> 160mmHg), unstable INR when taking vitamin K antagonists, or time for INR to reach the therapeutic target range value <60%, combined application increase Hemorrhage-prone drugs such as anti-platelet drugs and non-steroidal anti-inflammatory drugs, alcohol addiction (≥8 alcohol consumption/week)
.
Potentially correctable risk factors: anemia, impaired renal function (serum creatinine>200μmol/L), impaired liver function, decreased platelet count or function
.
Biomarkers of bleeding risk: high-sensitivity troponin, growth differentiation factor-15, serum creatinine/estimated creatinine clearance
.
Uncorrectable risk factors: age (greater than 65 years old), major bleeding, previous stroke, nephropathy requiring dialysis treatment, liver cirrhosis, malignant diseases, genetic factors
.
Treatment of vitamin K antagonist-related bleeding: mild bleeding: delay vitamin K antagonist until INR<2
.
Moderate to severe bleeding: need fluid replacement, correct the cause of bleeding, add vitamin K1
.
Severe: Need to combine prothrombin complex, fresh frozen plasma
.
The timing of restarting anticoagulation after bleeding is 4 weeks later
.
If the risk of atrial fibrillation embolism is high, and the cause of bleeding and related risk factors can be corrected, and the risk of new intracranial hemorrhage is low, anticoagulation can be started after 4 to 8 weeks; if the patient has both a high risk of bleeding and a risk of ischemia High, the left atrial appendage closure surgery can be performed on the patient to replace anticoagulation therapy
.
05How to treat ischemic stroke + atrial fibrillation + severe atherosclerosis? ①Stroke patients have both atrial fibrillation and atherosclerosis: anticoagulation or antiplaten? The 2019 AHA/ASA Guidelines for the Management of Patients with Acute Ischemic Stroke recommends: For patients with a history of ischemic stroke, atrial fibrillation, and coronary heart disease, add antiplatelet therapy to oral anticoagulants to reduce ischemia The benefit of the risk of sexual cardiovascular and cerebrovascular events is unclear
.
Indications for anticoagulation of atrial fibrillation: Both CHADS2 score and CHADS2-VASC score stipulate that as long as there is cerebral infarction/TIA, the score should be at least 2 points, and anticoagulation therapy is required
.
Anticoagulation is preferred, and antiplatelet drugs are not necessarily added at the same time
.
②Antithrombotic treatment after atrial fibrillation combined with percutaneous coronary intervention (PCI): double or triple? It is recommended that anticoagulation therapy be preferred, and antiplatelet therapy drugs may not be added at the same time, because it may increase the risk of bleeding
.
Consensus recommendations for antithrombotic therapy in patients with APSC atrial fibrillation in 2021: (1) Atrial fibrillation + elective PCI: direct oral anticoagulant (DOAC) + aspirin + clopidogrel triple antithrombotic for 1 month DOAC + clopidogrel double antithrombotic Long-term maintenance of DOAC single-agent anticoagulation for 6 months (2) Atrial fibrillation + acute coronary syndrome (ACS) (receiving PC): DOAC + aspirin + P2Y12 inhibitor triple antithrombotic to 1 month DOAC + P2Y12 inhibitor dual anticoagulant Long-term maintenance of DOAC single-agent anticoagulation for 12 months (3) Atrial fibrillation + ACS (drug therapy) DOAC+P2Y12 inhibitor dual antithrombotic to 12 months DOAC single-agent anticoagulation and long-term maintenance of stroke risk control for anticoagulation therapy When the rate is low, other treatment options: ATTEST study: radiofrequency ablation can reduce the risk of atrial fibrillation progression by 90%
.
In theory, sealing the left atrial appendage is one of the effective ways to prevent embolic complications in patients with atrial fibrillation
.
Summary: There are two main drug options for anticoagulation therapy in patients with ischemic stroke and atrial fibrillation: warfarin and NOAC.
The anticoagulation options for non-valvular atrial fibrillation and valvular atrial fibrillation are different, and anticoagulation is initiated after stroke.
The best time is 2-14 days after the onset of the disease.
When the anticoagulation treatment encounters bleeding, requires thrombolysis, antiplatelet therapy, etc.
, it is necessary to comprehensively evaluate the benefits and risks of the patient, and choose a reasonable treatment plan
.
For patients with ischemic stroke and atrial fibrillation, if the stroke risk control rate of anticoagulation therapy is low, radiofrequency ablation and left atrial appendage occlusion can also be considered
.
