Stroke prevention in patients with atrial fibrillation, as highlighted in the Asia Pacific Prevention Guidelines

Incidence of atrial fibrillation with aging population and prevalence is increasing and will continue to increase for decades to come. In Asian patients with atrial fibrillation, the annual risk of ischemic stroke is approximately 3.0% (1.60%–4.95%). Data show that with the clinical application of non-vitamin K antagonist oral anticoagulants (NOACs), the risk of ischemic stroke in newly diagnosed patients with atrial fibrillation has gradually decreased. Stroke prevention is specific to Asian patients with atrial fibrillation. Regarding the prevention of atrial fibrillation and stroke, the 2021Asia-Pacific Heart Rhythm Society (APHRS) guidelines give relevant recommendations.

Patients with atrial fibrillation usually have multiple diseases and cardiovascular risk factors, so comprehensive management is needed to improve the clinical prognosis of patients. The guidelines emphasize the use of the ABC management process:

• “A”: Use of anticoagulants to prevent stroke, with options for warfarin (TTR>65%-70%) or NOAC. NOACs are superior to warfarin in patients with atrial fibrillation who are eligible for NOACs.

• “B”: Use patient-centered, symptom-driven ventricular rate control or rhythm control decisions to better manage symptoms.

• “C”: Management of cardiovascular risk factors and comorbidities and lifestyle changes. Management of cardiovascular risk factors and comorbidities includes blood pressure control, heart failure/myocardial ischemia/sleep apnea management, etc.; lifestyle changes include obesity intervention, regular exercise, reduction of alcohol and stimulant intake, and psychological disease intervention.

Risk Assessment in Patients with Atrial Fibrillation

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1. Stroke risk assessment

It is recommended to use the CHA₂DS₂-VASc score to assess the risk of stroke in patients with atrial fibrillation, which is widely used in Asian populations has been fully verified. Stroke risk is not static and therefore requires periodic reassessment at follow-up. Based on available data, 4 months may be a reasonable interval to reassess stroke risk in patients with atrial fibrillation. Guidelines recommend reassessing stroke risk at least annually and every 4 months if possible. Stroke risk should ideally be reassessed at 4 months in patients with atrial fibrillation with a low initial stroke risk (CHA₂DS₂-VASc 0 for men and 1 for women). If the CHA₂DS₂-VASc score increases, oral anticoagulation should be initiated promptly. 2. Bleeding risk assessmentIt is recommended to use the HAS-BLED score for bleeding risk assessment to help identify unchangeable and Modifiable bleeding risk factors and identifying potentially high bleeding risk patients for earlier and more frequent follow-up. In the PCORI systematic review and evidence review, the HAS-BLED score was found to be the best score for predicting bleeding risk, and this score was well validated in an Asian cohort and outperformed other bleeding risk scores. Bleeding risk in patients with atrial fibrillation is also not constant and therefore requires periodic reassessment and correction of modifiable bleeding risk factors. In the absence of absolute contraindications to oral anticoagulants or a high risk of falls, an increased HAS-BLED score is not the only reason to discontinue oral anticoagulants, but should serve as a reminder for clinicians to Better follow-up and management of patients’ bleeding risk.

Anticoagulation to prevent stroke

1. Who should be anticoagulatedWhether anticoagulation should be performed mainly depends on the patient’s stroke risk factors, the type of atrial fibrillation (first time diagnosis, paroxysmal, persistent, long-term persistent or permanent) are not indicated for use. CHA₂DS₂-VASc score is ≥2 for males and ≥3 for females, and oral anticoagulation is recommended for stroke prevention; 1 for males and 2 for females, oral anticoagulation should be considered; for males 0, 1 point for women, the patient is at low risk of stroke, and antithrombotic therapy is not recommended. 2. What drug to chooseFor patients with atrial fibrillation with mechanical heart valves or moderate or severe mitral stenosis, Warfarin is recommended. For patients with atrial fibrillation without obvious valvular heart disease (mechanical heart valve or moderate or severe mitral stenosis, i.e. valvular atrial fibrillation) and who meet the indications for oral anticoagulants, NOACs are recommended for stroke prevention. The advantage of NOACs over vitamin K antagonists (VKAs) was more pronounced in Asian populations. In addition, the guidelines recommend that the CG equation be used to calculate the CCr to determine the NOAC dose. For Asian populations, it is recommended to use NOACs according to the instructions or guidelines. If warfarin is used, the recommended target INR is 2.0-3.0, TTR ≥ 65%, and ideal TTR ≥ 70%. A high SAMe-TT2R2 score (>2) may be associated with a lower TTR. For patients with INR within the therapeutic range for a short time (eg, TTR <70%), it is recommended to change from VKA to NOAC. In addition, left atrial appendage occlusion may be considered for stroke prevention in patients with atrial fibrillation who have clear contraindications to long-term anticoagulation, such as intracranial hemorrhage without a reversible cause. For patients with atrial fibrillation undergoing cardiac surgery, surgical closure of the left atrial appendage is recommended to prevent stroke.

Antithrombotic therapy in patients with atrial fibrillation and coronary heart disease

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In terms of bleeding, NOAC-based anticoagulation strategies are safer than warfarin-based strategies. For patients with atrial fibrillation who are candidates for NOAC, it is recommended to use NOAC in preference to VKA combined with antiplatelet drugs. For patients with high bleeding risk (HAS-BLED ≥ 3), the recommended dose of rivaroxaban is 15 mg qd and the recommended dose of dabigatran is 110 mg bid during concurrent single-agent antiplatelet or dual antiplatelet therapy. For patients with atrial fibrillation who are indicated for VKA combined with antiplatelet drugs, the dose of VKA should be carefully adjusted, with a target INR of 2.0-2.5 and TTR>70%. In patients with acute coronary syndrome and atrial fibrillation undergoing uncomplicated PCI, early discontinuation of aspirin is recommended if the risk of stent thrombosis is low, or if the risk of bleeding outweighs the risk of stent thrombosis (≤1 week), continue treatment with oral anticoagulants and a P2Y₁₂ inhibitor (preferably clopidogrel) for up to 12 months. When the risk of stent thrombosis exceeds the risk of bleeding, triple therapy with aspirin, clopidogrel, and oral anticoagulants should be considered for more than 1 week after acute coronary syndrome, and the total course of treatment should be within 1 month. risk to be assessed. After 1 year, oral anticoagulants were used alone. In patients with stable coronary artery disease undergoing uncomplicated, elective PCI, early discontinuation of aspirin ( ≤1 week), continue treatment with oral anticoagulants and clopidogrel for up to 6 months, regardless of the patient’s stent. When the risk of stent thrombosis exceeds the risk of bleeding, triple therapy with aspirin, clopidogrel, and oral anticoagulants should be considered for more than 1 week, and the total course of treatment should be within 1 month. After 6 months, oral anticoagulants were used alone. Standard-dose NOAC monotherapy is recommended for patients with stable coronary artery disease, such as more than 1 year after PCI or CABG.

Perioperative oral anticoagulant therapy for atrial fibrillation ablation

In the perioperative period of atrial fibrillation ablation, NOACs are preferred as anticoagulants because they are safer and easier to manage than VKAs. No or minimal interruptions should be determined based on the volume of ablation for atrial fibrillation, operator experience, complication management conditions, baseline renal function, thromboembolic and bleeding risk, duration of NOAC administration, and specific antidote status NOAC policy. For most patients, an uninterrupted NOAC strategy may be the first choice.

When VKAs are used, they should be controlled within the therapeutic range and administered uninterrupted throughout the perioperative period unless bleeding events prevent their continued use. In general, all patients received oral anticoagulation for 2 months after ablation. The continuation of long-term oral anticoagulant use thereafter depends on the CHA₂DS₂-VASc score, not heart rhythm status.

NOAC Reversal Drugs

For severe or life-threatening bleeding, a reversal agent may be considered to reverse the anticoagulant effect of NOACs. Idarucizumab can be used to reverse anticoagulation in patients receiving dabigatran who experience severe bleeding or require urgent surgery. Although both dabigatran and idacilizumab were renally cleared, impaired renal function did not affect reversal of anticoagulation. In patients receiving factor Xa inhibitors, andexanet alfa can be used to reverse anticoagulation if bleeding is life-threatening or uncontrolled.

For patients with oral anticoagulant-related bleeding, occult malignancies may be the underlying cause of bleeding. For example, gastrointestinal bleeding may be caused by gastrointestinal tumors. Patients with later hematuria should be evaluated for the possibility of bladder cancer.

Lifestyle Interventions

Cardiovascular Risk factors, including lifestyle factors and comorbidities, influence the risk and prognosis of atrial fibrillation. Management of these risk factors, unhealthy lifestyle/behavior, and comorbidities is important for stroke prevention and control of AF burden and AF-related symptoms. Lifestyle modifications (weight loss, physical activity, alcohol abstinence) and risk factor management (including blood pressure control) have been shown to reduce the burden of atrial fibrillation.

The guidelines recommend promoting a healthy lifestyle to reduce the risk of new-onset atrial fibrillation and complications associated with atrial fibrillation, such as quitting smoking, reducing alcohol intake, and exercising regularly. Appropriate weight control is an important strategy to improve the prognosis of patients with atrial fibrillation. Patients with atrial fibrillation are advised to abstain from or reduce alcohol consumption to reduce the burden of atrial fibrillation and stroke risk; smoking cessation is recommended to reduce stroke risk, even in patients classified as low risk by the CHA₂DS₂-VASc score. 150 minutes of moderate-intensity exercise or 75 minutes of vigorous exercise per week is recommended to improve cardiovascular outcomes in patients with atrial fibrillation.

Management of Atrial Fibrillation Anticoagulation During the COVID-19 Epidemic

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During the COVID-19 epidemic, NOACs can be considered in place of VKAs (inconvenient to monitor INR) in outpatient AF patients, unless the patient has contraindications. For patients with atrial fibrillation who are treated with NOAC or VKA and infected with new coronary pneumonia, especially those with severe infection during hospitalization or intensive care (requiring some antiviral drugs), consider switching to low molecular weight heparin, Reduce drug interactions.

For patients with atrial fibrillation who are taking NOACs and are scheduled to receive the COVID-19 vaccine, NOAC dose adjustments are not required before and after vaccination. It is recommended to use a thin needle when injecting the vaccine, and press firmly for 5-10 minutes after injection. Bibliography: Tze-Fan Chao, Boyoung Joung, Yoshihide Takahashi, et al. 2021 Focused Update Consensus Guidelines of the Asia Pacific Heart Rhythm Society on Stroke Prevention in Atrial Fibrillation: Executive Summary. Thromb Haemost. 2021 Nov 13. doi: 10.1055/s-0041-1739411. Online ahead of print.