Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

paroxysmal or persistent AF: hemodynamically unstable

1st line – direct current (DC) cardioversion

Back
ACUTE
|
paroxysmal or persistent AF: hemodynamically unstable
1st line – 

direct current (DC) cardioversion

Patients with established atrial fibrillation (AF) may present acutely with hemodynamic instability. AF with a rapid ventricular rate causing ongoing chest pain, hypotension, shortness of breath, dizziness, or syncope requires immediate direct current (DC) cardioversion.[3]

DC cardioversion is performed under adequate short-acting general anesthesia and involves delivery of an electrical shock synchronized with the intrinsic activity of the heart by sensing the R wave of the ECG (i.e., synchronized). Most currently used external defibrillators utilize biphasic energy, 100-360 J, depending on body size and the presence of other comorbid conditions.

Imaging to rule out the presence of a clot should be considered whenever possible before cardioversion, in those at higher thromboembolic risk, or unknown anticoagulation profile.[1] AF that is asymptomatic before the immediate event is common, making a determination of the duration uncertain..​

ONGOING

paroxysmal or persistent AF and hemodynamically stable: rate-control strategy selected

1st line – pharmacologic rate control

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rate-control strategy selected
|
no contraindications to long-term anticoagulation
1st line – 

pharmacologic rate control

A rate-control strategy may be preferred over rhythm control in older patients who have a longer history of atrial fibrillation (AF) and fewer symptoms, and in whom likelihood of successful restoration of sinus rhythm would be deemed low, such as in patients with very large left atrium.[1][2]​​​​

Aggressive rate control with pharmacologic agents may result in significant depression of the left ventricular (LV) systolic function. A lenient rate-control strategy (resting heart rate <110 bpm) may be reasonable as long as patients remain asymptomatic and left ventricular systolic function is preserved.[1][2]​​​​

Patients with paroxysmal/persistent AF with rapid ventricular response requiring acute rate control are treated with either a beta-blocker, a nondihydropyridine calcium-channel blocker (diltiazem or verapamil, if ejection fraction [EF] >40%), digoxin, or amiodarone.[1][2]

Choice of therapy is determined by presence of comorbidities, presence or absence of heart failure, and left ventricular EF. When left ventricular function is preserved, a beta-blocker or nondihydropyridine calcium-channel blocker is preferred. Digoxin is not considered a first-line agent for the purpose of rate control, but it can be useful (either alone or in combination) when beta-blockers and nondihydropyridine calcium-channel blockers are ineffective or contraindicated. Amiodarone may be considered for acute rate control in patients who are critically ill when beta-blockers and nondihydropyridine calcium-channel blockers are ineffective or contraindicated.[1][2]

Beta-blockers and nondihydropyridine calcium-channel blockers (if EF >40%) may also be used for long-term rate control, with digoxin considered either alone or in combination if other options are not tolerated or contraindicated.[1][2]

Considerations for patients with comorbid HF: in patients with AF and HF with preserved EF (HFpEF; EF >40%), a beta-blocker or nondihydropyridine calcium-channel blocker is preferred for rate control. Nondihydropyridine calcium-channel blockers must not be used in patients with HF with reduced EF (HFrEF; EF ≤40%) owing to their negative inotropic effect. Digoxin is an alternative option for rate control in patients with AF and either HFpEF or HFrEF. Amiodarone may be considered for acute rate control in patients with decompensated HF when beta-blockers and nondihydropyridine calcium-channel blockers are ineffective or contraindicated. The optimal target heart rate in patients with AF and HF is unclear.

Considerations for patients with comorbid pulmonary disease: cardioselective beta-blockers (e.g., atenolol, bisoprolol, metoprolol) may be used for rate control in patients with AF and COPD (other rate control agents may also be used, but beta-blockers do not need to be avoided). Beta-blockers should be avoided in patients with reactive airway disease, such as asthma.[1]

Considerations for patients with comorbid cancer: patients with AF and cancer should be managed by a multidisciplinary team. Treatments for AF may be less effective if it is caused directly by the cancer therapy.[59]​ Drug-drug interactions can occur between cancer therapies and AF therapies. Beta-blockers are preferred for rate control in patients with cancer and AF, particularly if the cancer therapies have potential cardiovascular risk; diltiazem and verapamil should be avoided due to associations with negative inotropic effects and drug-drug interactions.[59]

Primary options

metoprolol tartrate: 25-200 mg orally (immediate-release) twice daily

OR

propranolol hydrochloride: 10-40 mg orally (immediate-release) three to four times daily

OR

atenolol: : 25-100 mg orally once daily

OR

nadolol: 10-240 mg orally once daily

OR

bisoprolol: 2.5 to 10 mg orally once daily

OR

carvedilol: 3.125 to 25 mg orally twice daily

OR

diltiazem: 120-360 mg orally (extended-release) once daily

OR

verapamil: 180-480 mg orally (extended-release) once daily

Secondary options

digoxin: 0.25 to 0.5 mg intravenously as a loading dose, followed by 0.25 mg every 6 hours (maximum 1.5 mg/24 hours), then 0.0625 to 0.25 mg orally once daily

OR

amiodarone: 150-300 mg intravenously as a loading dose, followed by 10-50 mg/hour infusion over 24 hours, then 100-200 mg orally once daily

More

Plus – estimate stroke risk and consider anticoagulation

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rate-control strategy selected
|
no contraindications to long-term anticoagulation
Plus – 

estimate stroke risk and consider anticoagulation

Treatment recommended for ALL patients in selected patient group

Risk of stroke and thromboembolic events should be assessed in all patients using a validated clinical risk score, such as the CHA₂DS₂-VASc tool.[1][2][78]​​​ Guidelines from the American College of Cardiology/American Heart Association/American Association of Colleges of Pharmacy/Heart Rhythm Society (ACC/AHA/ACCP/HRS) recommend that the risk is evaluated annually.[1]

The CHA₂DS₂-VASc tool is the most validated risk score and is most widely used.[1][2][78]​​​​​ CHA₂DS₂-VASc allocates 1 point each for chronic heart failure, hypertension, age 65-74 years, diabetes mellitus, vascular disease, and female sex, and 2 points each for a history of stroke or transient ischemic attack, or age 75 years and older.[99] [ Atrial Fibrillation CHA(2)DS(2)-VASc Score for Stroke Risk Opens in new window ] ​​​​ The ACC/AHA/ACCP/HRS and ESC guidelines recommend the use of oral anticoagulants for patients with AF and a CHA₂DS₂-VASc score of ≥2 in men or ≥3 in women (1 for gender, and 2 for additional risk factors), which corresponds to annual thromboembolic risk of ≥2%.[1][2]​​​​​ With a score of ≥1 in men or ≥2 in women (1 for gender and 1 for additional risk factors; corresponds to annual risk of ≥1% to <2%), the use of oral anticoagulants to prevent thromboembolic stroke can be considered; additional factors that may modify stroke risk, such as hypertension control, can be taken into account.[1][2]​​​​​ Use of oral anticoagulants in patients with a nonsex-related CHA₂DS₂-VASc score of 1 is particularly important to consider in patients over the age of 65 years.[3]

Use of any anticoagulation strategy needs to be balanced with the risk of bleeding, particularly intracranial bleeding.[100] Scoring systems such as ORBIT, HAS-BLED, HEMORR₂HAGES, and the newer direct oral anticoagulant (DOAC) score can help to quantify this risk and assess how the bleeding risk can be minimized.[101] MdCalc: HEMORR₂HAGES Score for Major Bleeding Risk​ Opens in new window​​​​​​​​​​ [ ORBIT Bleeding Risk Score Opens in new window ] [ HAS-BLED Bleeding Risk Score Opens in new window ] ​​​​​​​​​ When used in combination with a stroke risk score such as CHA₂DS₂-VASc, bleeding risk tools provide a means to balance the benefits and risks of anticoagulation with patients. Bleeding risk scores should not be used to exclude people from receiving anticoagulant treatment.[1][2][102]​​​​​​​

In patients with cardiac implantable electronic devices, AF may be detected as atrial high rate episodes (AHRE), which can be silent/asymptomatic. Anticoagulation therapy for prevention of thromboembolism and stroke based on subclinical AF has not shown to be convincingly useful; use of DOACs in the ARTESIA and NOAH-AF trials was associated with increased risk of major bleeding.[103][104]​​ In patients who have longer duration AHREs, are at higher risk of stroke (e.g., measured by CHA₂DS₂-VASc), and have symptomatic AF, anticoagulation may be of benefit.[1][2][105]

Oral anticoagulation drugs for stroke prevention are warfarin or a DOAC such as dabigatran, rivaroxaban, apixaban, or edoxaban. All patients should preferably be started on a DOAC, unless they are not eligible (e.g., presence of moderate to severe mitral valve stenosis or mechanical prosthetic valves) or DOACs are not available.[1][2][78]​ DOACs are generally safe in older patients; however, dabigatran may be associated with an increased risk of gastrointestinal bleeding compared with warfarin.[117]

If DOACs are used in patients with renal impairment, they should be used with caution. Some DOACs may require dose adjustment and some contraindicated. Consult a drug information source for specific guidance on use in patients with renal impairment. DOACs should not be used in combination with heparin (including low molecular weight heparin [LMWH]), heparin derivatives, or warfarin.

The efficacy and safety of anticoagulation with warfarin is highly dependent on the quality of anticoagulation control as reflected by the average time in therapeutic range (TTR) of INR 2 to 3. The SAMe-TT₂R₂ scoring system (based on sex, age, medical history, treatment interactions, tobacco use, and race) is a tool that may help identify anticoagulation-naive patients who are less likely to maintain TTR >70% and who should, therefore, be managed with DOACs instead of warfarin.[118][119] SAMe-TT₂R₂ score Opens in new window​​​​​​​

Recommendations for anticoagulation in patients with concomitant conditions, are available and should be consulted.[1][2]​​​

Concomitant surgical LAA exclusion may be considered (in addition to continued anticoagulation) in patients with a CHA₂DS₂-VASc score ≥2 or equivalent stroke risk who are undergoing cardiac surgery (e.g., coronary artery bypass graft or valve surgery).[1]

The ACC/AHA/ACCP/HRS, ESC, and NICE (UK) guidelines do not recommend aspirin as an alternative to anticoagulation for stroke prevention in patients with AF.[1][2][78]​​​ 

Considerations for patients with comorbid obesity: DOACs may be used over warfarin in those with class III obesity (BMI ≥40 kg/m²). Warfarin may be preferred in those who have undergone bariatric surgery.[1]

Considerations for patients with comorbid diabetes: DOACs are associated with reduced vascular mortality compared with warfarin in those with AF and diabetes.[1][2]​ 

Considerations for patients with comorbid valvular heart disease (VHD): the US guidelines recommend that patients with AF and significant (moderate or greater) mitral stenosis or a mechanical heart valve should receive long-term anticoagulation regardless of CHA₂DS₂-VASc score.[1]​ Warfarin is recommended over DOACs in these patients.[1][2]​ In patients with AF and other comorbid VHD (i.e., not moderate-to-severe mitral stenosis or a mechanical heart valve), DOACs may be used over warfarin.[1][2]

Considerations for patients with comorbid chronic kidney disease (CKD): renal function must be considered when selecting an anticoagulant regimen. Some drugs should be used with caution in patients with renal impairment and a dose adjustment may be required. Some drugs may also be contraindicated in patients with renal impairment. Check your local drug information source for more information. The US guidelines advise that patients with stage 3 CKD may receive either a DOAC (preferred) or warfarin; patients with stage 4 CKD may reasonably receive either warfarin or a DOAC; and patients with end-stage CKD (CrCl <15 mL/min) or who are on dialysis may reasonably receive warfarin or apixaban.[1]​ In Europe, DOACs are not approved for patients with CrCl ≤15 mL/min or on dialysis.[2]

Considerations for patients with comorbid liver disease: in those with mild or moderate liver disease (Child-Pugh score A or B), DOACs may be used over warfarin; however, rivaroxaban should not be used in moderate liver disease (Child-Pugh B).[1][2]​ There are no data on use of DOACs in patients with severe liver disease (Child-Pugh class C). In Europe, DOACs are contraindicated in these patients.[1][2]​ Warfarin may be used in patients with Child-Pugh class C liver disease; in high-risk patients (recent major bleeding, active coagulopathy, severe thrombocytopenia, or high-risk varices not amenable to intervention) decision to use is individualized.[184]

Considerations for patients with comorbid hypertrophic cardiomyopathy (HCM): patients with HCM and AF should receive long-term anticoagulation regardless of CHA₂DS₂-VASc score.[1]​ The US guidelines recommend DOACs as the preferred option in patients with HCM and AF, and warfarin as the second-line alternative.[185]

Considerations for patients with comorbid cancer: patients with AF and cancer should be managed by a multidisciplinary team. When choosing an anticoagulant in patients with cancer and AF, the cancer type, status, and prognosis, as well as the patient’s bleeding/thromboembolic risk should all be considered. DOACs are recommended as first-line in patients without a high bleeding risk, severe renal dysfunction, or significant drug-drug interactions. LMWH (not detailed here) can be considered in patients who have active cancer and AF but are not suitable for DOACs.[59]

Adult congenital heart disease (ACHD): some patients with moderate or complex CHD (e.g., Fontan circulation, cyanosis) are at higher risk for thromboembolic events and anticoagulation may be indicated regardless of usual AF risk score.[1][2]​ 

Primary options

dabigatran etexilate: 150 mg orally twice daily

OR

apixaban: 2.5 to 5 mg orally twice daily

OR

edoxaban: 60 mg orally once daily

OR

rivaroxaban: 20 mg orally once daily

OR

warfarin: 2-5 mg orally once daily initially, adjust dose according to target INR

More

Plus – lifestyle and risk factor modification

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rate-control strategy selected
|
no contraindications to long-term anticoagulation
Plus – 

lifestyle and risk factor modification

Treatment recommended for ALL patients in selected patient group

All patients with atrial fibrillation (AF) should receive comprehensive guideline-directed lifestyle and risk factor modification, which includes maintenance of ideal weight and weight loss if overweight or obese (the US guidelines recommend an ideal target weight of at least 10% weight loss); having a physically active lifestyle; reducing unhealthy alcohol consumption; stopping smoking; controlling diabetes; and controlling blood pressure/hypertension.[1]

Patients with AF should also have their risk factors for sleep-disordered breathing (SDB) considered, and screening, diagnosis, and management of SDB provided where indicated.[43]

2nd line – atrioventricular node ablation (AVNA) and pacing

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rate-control strategy selected
|
no contraindications to long-term anticoagulation
2nd line – 

atrioventricular node ablation (AVNA) and pacing

AVNA and pacemaker implantation may be considered for rate control when rapid ventricular response is refractory to pharmacologic rate control and attempt at rhythm control has either been unsuccessful, or the patient is not eligible for rhythm control.[1][2]

Plus – estimate stroke risk and consider anticoagulation

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rate-control strategy selected
|
no contraindications to long-term anticoagulation
Plus – 

estimate stroke risk and consider anticoagulation

Treatment recommended for ALL patients in selected patient group

Risk of stroke and thromboembolic events should be assessed in all patients using a validated clinical risk score, such as the CHA₂DS₂-VASc tool.[1][2][78]​​​ Guidelines from the American College of Cardiology/American Heart Association/American Association of Colleges of Pharmacy/Heart Rhythm Society (ACC/AHA/ACCP/HRS) recommend that the risk is evaluated annually.[1]

The CHA₂DS₂-VASc tool is the most validated risk score and is most widely used.[1][2][78]​​​​ CHA₂DS₂-VASc allocates 1 point each for chronic heart failure, hypertension, age 65 to 74 years, diabetes mellitus, vascular disease, and female sex, and 2 points each for a history of stroke or transient ischemic attack, or age 75 years and older.[99] [ Atrial Fibrillation CHA(2)DS(2)-VASc Score for Stroke Risk Opens in new window ] ​​​ The ACC/AHA/ACCP/HRS and ESC guidelines recommend the use of oral anticoagulants for patients with AF and a CHA₂DS₂-VASc score of ≥2 in men or ≥3 in women (1 for gender, and 2 for additional risk factors), which corresponds to annual thromboembolic risk of ≥2%.[1][2]​​​​ With a score of ≥1 in men or ≥2 in women (1 for gender and 1 for additional risk factors; corresponds to annual risk of ≥1% to <2%), the use of oral anticoagulants to prevent thromboembolic stroke can be considered; additional factors that may modify stroke risk, such as hypertension control, can be taken into account.[1][2]​​​​ Use of oral anticoagulants in patients with a nonsex-related CHA₂DS₂-VASc score of 1 is particularly important to consider in patients over the age of 65 years.[3]

Use of any anticoagulation strategy needs to be balanced with the risk of bleeding, particularly intracranial bleeding.[100] Scoring systems such as ORBIT, HAS-BLED, HEMORR₂HAGES, and the newer DOAC score can help to quantify this risk and assess how the bleeding risk can be minimized.[101] MdCalc: HEMORR₂HAGES Score for Major Bleeding Risk​ Opens in new window​​​​​​​​​​ [ ORBIT Bleeding Risk Score Opens in new window ] [ HAS-BLED Bleeding Risk Score Opens in new window ] ​​​​​​​​​ When used in combination with a stroke risk score such as CHA₂DS₂-VASc, bleeding risk tools provide a means to balance the benefits and risks of anticoagulation with patients. Bleeding risk scores should not be used to exclude people from receiving anticoagulant treatment.[1][2][102]​​​​​​​

In patients with cardiac implantable electronic devices, AF may be detected as AHRE, which can be silent/asymptomatic. Anticoagulation therapy for prevention of thromboembolism and stroke based on subclinical AF has not shown to be convincingly useful; use of DOACs in the ARTESIA and NOAH-AF trials was associated with increased risk of major bleeding.[103][104]​​ In patients who have longer duration AHREs, are at higher risk of stroke (e.g., measured by CHA₂DS₂-VASc), and have symptomatic AF, anticoagulation may be of benefit.[1][2][105]

Oral anticoagulation drugs for stroke prevention are warfarin or a DOAC such as dabigatran, rivaroxaban, apixaban, or edoxaban. All patients should preferably be started on a DOAC, unless they are not eligible (e.g., presence of moderate to severe mitral valve stenosis or mechanical prosthetic valves) or DOACs are not available.[1][2][78]​ DOACs are generally safe in older patients; however, dabigatran may be associated with an increased risk of gastrointestinal bleeding compared with warfarin.[117]

If DOACs are used in patients with renal impairment, they should be used with caution. Some DOACs may require dose adjustment and some may be contraindicated. Consult a drug information source for specific guidance on use in patients with renal impairment. DOACs should not be used in combination with heparin (including LMWH), heparin derivatives, or warfarin.

The efficacy and safety of anticoagulation with warfarin is highly dependent on the quality of anticoagulation control as reflected by the average time in therapeutic range (TTR) of INR 2 to 3. The SAMe-TT₂R₂ scoring system (based on sex, age, medical history, treatment interactions, tobacco use, and race) is a tool that may help identify anticoagulation-naive patients who are less likely to maintain TTR >70% and who should, therefore, be managed with DOACs instead of warfarin.[118][119] SAMe-TT₂R₂ score Opens in new window​​​​​​

Recommendations for anticoagulation in patients with concomitant condition are available and should be consulted.[1][2]​​​

Concomitant surgical LAA exclusion may be considered (in addition to continued anticoagulation) in patients with a CHA₂DS₂-VASc score ≥2 or equivalent stroke risk who are undergoing cardiac surgery (e.g., coronary artery bypass graft or valve surgery).[1]

The ACC/AHA/ACCP/HRS, ESC, and NICE (UK) guidelines do not recommend aspirin as an alternative to anticoagulation for stroke prevention in patients with AF.[1][2][78]​​​ 

Considerations for patients with comorbid obesity: DOACs may be used over warfarin in those with class III obesity (BMI ≥40 kg/m²). Warfarin may be preferred in those who have undergone bariatric surgery.[1]

Considerations for patients with comorbid diabetes: DOACs are associated with reduced vascular mortality compared with warfarin in those with AF and diabetes.[1][2]

Considerations for patients with comorbid VHD: the US guidelines recommend that patients with AF and significant (moderate or greater) mitral stenosis or a mechanical heart valve should receive long-term anticoagulation regardless of CHA₂DS₂-VASc score.[1]​ Warfarin is recommended over DOACs in these patients.[1][2]​ In patients with AF and other comorbid VHD (i.e., not moderate-to-severe mitral stenosis or a mechanical heart valve), DOACs may be used over warfarin.[1][2]​ 

Considerations for patients with comorbid CKD: renal function must be considered when selecting an anticoagulant regimen. Some drugs should be used with caution in patients with renal impairment and a dose adjustment may be required. Some drugs may also be contraindicated in patients with renal impairment. Check your local drug information source for more information. The US guidelines advise that patients with stage 3 CKD may receive either a DOAC (preferred) or warfarin; patients with stage 4 CKD may reasonably receive either warfarin or a DOAC; and patients with end-stage CKD (CrCl <15 mL/min) or who are on dialysis may reasonably receive warfarin or apixaban.[1]​ In Europe, DOACs are not approved for patients with CrCl ≤15 mL/min or on dialysis.[2]

Considerations for patients with comorbid liver disease: in those with mild or moderate liver disease (Child-Pugh score A or B), DOACs may be used over warfarin; however, rivaroxaban should not be used in moderate liver disease (Child-Pugh B).[1][2]​ There are no data on use of DOACs in patients with severe liver disease (Child-Pugh class C). In Europe, DOACs are contraindicated in these patients.[1][2]​ Warfarin may be used in patients with Child-Pugh class C liver disease; in high-risk patients (recent major bleeding, active coagulopathy, severe thrombocytopenia, or high-risk varices not amenable to intervention) decision to use is individualized.[184]

Considerations for patients with comorbid HCM: patients with HCM and AF should receive long-term anticoagulation regardless of CHA₂DS₂-VASc score.[1]​ The US guidelines recommend DOACs as the preferred option in patients with HCM and AF, and warfarin as the second-line alternative.[185]

Considerations for patients with comorbid cancer: patients with AF and cancer should be managed by a multidisciplinary team. When choosing an anticoagulant in patients with cancer and AF, the cancer type, status, and prognosis, as well as the patient’s bleeding/thromboembolic risk should all be considered. DOACs are recommended as first-line in patients without a high bleeding risk, severe renal dysfunction, or significant drug-drug interactions. LMWH (not detailed here) can be considered in patients who have active cancer and AF but are not suitable for DOACs.[59]

ACHD: Some patients with moderate or complex CHD (e.g., Fontan circulation, cyanosis) are at higher risk for thromboembolic events and anticoagulation may be indicated regardless of usual AF risk score.[1][2]

Primary options

dabigatran etexilate: 150 mg orally twice daily

OR

apixaban: 2.5 to 5 mg orally twice daily

OR

edoxaban: 60 mg orally once daily

OR

rivaroxaban: 20 mg orally once daily

OR

warfarin: 2-5 mg orally once daily initially, adjust dose according to target INR

More

Plus – lifestyle and risk factor modification

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rate-control strategy selected
|
no contraindications to long-term anticoagulation
Plus – 

lifestyle and risk factor modification

Treatment recommended for ALL patients in selected patient group

All patients with atrial fibrillation (AF) should receive comprehensive guideline-directed lifestyle and risk factor modification, which includes maintenance of ideal weight and weight loss if overweight or obese (the US guidelines recommend an ideal target weight of at least 10% weight loss); having a physically active lifestyle; reducing unhealthy alcohol consumption; stopping smoking; controlling diabetes; and controlling blood pressure/hypertension.[1]

Patients with AF should also have their risk factors for sleep-disordered breathing (SDB) considered, and screening, diagnosis, and management of SDB provided where indicated.[43]

1st line – pharmacologic rate control

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rate-control strategy selected
|
contraindications to long-term anticoagulation
1st line – 

pharmacologic rate control

A rate-control strategy may be preferred over rhythm control in older patients who have a longer history of atrial fibrillation (AF) and fewer symptoms.[1][2]​​​ Additionally, rate control is also generally preferred in patients who have a larger left atrium, less left ventricular dysfunction, less atrioventricular regurgitation, and an easily controlled heart rate.

Aggressive rate control with pharmacologic agents may result in significant depression of the left ventricular systolic function. In some patients who have slow resting heart rates, drug therapy could be hazardous. A lenient rate-control strategy (resting heart rate <110 bpm) may be reasonable as long as patients remain asymptomatic and left ventricular systolic function is preserved.

Patients with paroxysmal/persistent AF with rapid ventricular response requiring acute rate control are treated with either a beta-blocker, a nondihydropyridine calcium-channel blocker (diltiazem or verapamil, if ejection fraction [EF] >40%), digoxin, or amiodarone.[1][2]

Choice of therapy is determined by presence of comorbidities, presence or absence of heart failure, and left ventricular EF. When left ventricular function is preserved, a beta-blocker or nondihydropyridine calcium-channel blocker is preferred. Digoxin is not considered a first-line agent for the purpose of rate control, but it can be useful (either alone or in combination) when beta-blockers and nondihydropyridine calcium-channel blockers are ineffective or contraindicated. Amiodarone may be considered for acute rate control in patients who are critically ill when beta-blockers and nondihydropyridine calcium-channel blockers are ineffective or contraindicated.[1][2]

Beta-blockers and nondihydropyridine calcium-channel blockers (if EF >40%) may also be used for long-term rate control, with digoxin considered either alone or in combination if other options are not tolerated or contraindicated.[1][2]

Considerations for patients with comorbid HF: in patients with AF and HF with preserved EF (HFpEF; EF >40%), a beta-blocker or nondihydropyridine calcium-channel blocker is preferred for rate control. Nondihydropyridine calcium-channel blockers must not be used in patients with HF with reduced EF (HFrEF; EF ≤40%) owing to their negative inotropic effect. Digoxin is an alternative option for rate control in patients with AF and either HFpEF or HFrEF. Amiodarone may be considered for acute rate control in patients with decompensated HF when beta-blockers and nondihydropyridine calcium-channel blockers are ineffective or contraindicated. The optimal target heart rate in patients with AF and HF is unclear.

Considerations for patients with comorbid pulmonary disease: cardioselective beta-blockers (e.g., atenolol, bisoprolol, metoprolol) may be used for rate control in patients with AF and COPD (other rate control agents may also be used, but beta-blockers do not need to be avoided). Beta-blockers should be avoided in patients with reactive airway disease, such as asthma.[1]

Considerations for patients with comorbid cancer: patients with AF and cancer should be managed by a multidisciplinary team. Treatments for AF may be less effective if it is caused directly by the cancer therapy.[59]​ Drug-drug interactions can occur between cancer therapies and AF therapies. Beta-blockers are preferred for rate control in patients with cancer and AF, particularly if the cancer therapies have potential cardiovascular risk; diltiazem and verapamil should be avoided due to associations with negative inotropic effects and drug-drug interactions.[59]

Primary options

metoprolol tartrate: 25-200 mg orally (immediate-release) twice daily

OR

propranolol hydrochloride: 10-40 mg orally (immediate-release) three to four times daily

OR

atenolol: 25-100 mg orally once daily

OR

nadolol: 10-240 mg orally once daily

OR

bisoprolol: 2.5 to 10 mg orally once daily

OR

carvedilol: 3.125 to 25 mg orally twice daily

OR

diltiazem: 120-360 mg orally (extended-release) once daily

OR

verapamil: 180-480 mg orally (extended-release) once daily

Secondary options

digoxin: 0.25 to 0.5 mg intravenously as a loading dose, followed by 0.25 mg every 6 hours (maximum 1.5 mg/24 hours), then 0.0625 to 0.25 mg orally once daily

OR

amiodarone: 150-300 mg intravenously as a loading dose, followed by 10-50 mg/hour infusion over 24 hours, then 100-200 mg orally once daily

More

Plus – estimate stroke risk and consider left atrial appendage occlusion

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rate-control strategy selected
|
contraindications to long-term anticoagulation
Plus – 

estimate stroke risk and consider left atrial appendage occlusion

Treatment recommended for ALL patients in selected patient group

Risk of stroke and thromboembolic events should be assessed in all patients using a validated clinical risk score, such as the CHA₂DS₂-VASc tool.[1][2][78]

Left atrial appendage occlusion (LAAO) may be considered as an alternative for stroke prevention when there are absolute contraindications to use of anticoagulants, or the risk of bleeding outweighs the benefits.[1][2][78][123][124]​​ LAAO devices such as the WATCHMAN™ and the Amplatzer™ Cardiac Plug device may be implanted percutaneously via transeptal catheterization. In the PROTECT AF trial, the primary efficacy event rate (a composite end point of stroke, cardiovascular death, and systemic embolism) of the WATCHMAN™ device was considered noninferior to that of warfarin.[125]​ There was a higher rate of adverse safety events in the intervention group than in the control group due mainly to periprocedural complications. The Amplatzer™ Cardiac Plug consists of a small proximal disk, a central polyester patch, and a larger distal disk with hooks to anchor the device in the LAA. It does not require anticoagulation and a European trial found a 96% success rate for deployment/implantation but with a 7% incidence of serious complications.[126]​ Another nonpharmacologic approach to isolate and occlude LAA is to tie off the LAA using the LARIAT device, which is an epicardial snare.[127]​ The WATCHMAN FLX™ device is a next-generation LAA closure device that has a greater number of struts and dual-row J-shaped anchors to maximize device stability. A prospective, nonrandomized, multicenter study (PINNACLE FLX) found the WATCHMAN FLX™ to be associated with a low incidence of adverse events and a high incidence of anatomic closure.[128]

Concomitant surgical LAA exclusion may be considered (in addition to continued anticoagulation) in patients with a CHA₂DS₂-VASc score ≥2 or equivalent stroke risk who are undergoing cardiac surgery (e.g., coronary artery bypass graft or valve surgery).[1]

Plus – lifestyle and risk factor modification

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rate-control strategy selected
|
contraindications to long-term anticoagulation
Plus – 

lifestyle and risk factor modification

Treatment recommended for ALL patients in selected patient group

All patients with atrial fibrillation (AF) should receive comprehensive guideline-directed lifestyle and risk factor modification, which includes maintenance of ideal weight and weight loss if overweight or obese (the US guidelines recommend an ideal target weight of at least 10% weight loss); having a physically active lifestyle; reducing unhealthy alcohol consumption; stopping smoking; controlling diabetes; and controlling blood pressure/hypertension.[1]

Patients with AF should also have their risk factors for sleep-disordered breathing (SDB) considered, and screening, diagnosis, and management of SDB provided where indicated.[43]

2nd line – atrioventricular node ablation (AVNA) and pacing

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rate-control strategy selected
|
contraindications to long-term anticoagulation
2nd line – 

atrioventricular node ablation (AVNA) and pacing

​AVNA and pacemaker implantation may be considered for rate control when rapid ventricular response is refractory to pharmacologic rate control and attempt at rhythm control has either been unsuccessful, or the patient is not eligible for rhythm control.[1][2]

Plus – estimate stroke risk and consider left atrial appendage occlusion

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rate-control strategy selected
|
contraindications to long-term anticoagulation
Plus – 

estimate stroke risk and consider left atrial appendage occlusion

Treatment recommended for ALL patients in selected patient group

Risk of stroke and thromboembolic events should be assessed in all patients using a validated clinical risk score, such as the CHA₂DS₂-VASc tool.[1][2][78]

Left atrial appendage occlusion (LAAO) may be considered as an alternative for stroke prevention when there are absolute contraindications to use of anticoagulants, or the risk of bleeding outweighs the benefits.[1][2][78][123][124]​​ LAAO devices such as the WATCHMAN™ and the Amplatzer™ Cardiac Plug device may be implanted percutaneously via transeptal catheterization. In the PROTECT AF trial, the primary efficacy event rate (a composite end point of stroke, cardiovascular death, and systemic embolism) of the WATCHMAN™ device was considered noninferior to that of warfarin.[125]​ There was a higher rate of adverse safety events in the intervention group than in the control group due mainly to periprocedural complications. The Amplatzer™ Cardiac Plug consists of a small proximal disk, a central polyester patch, and a larger distal disk with hooks to anchor the device in the LAA. It does not require anticoagulation and a European trial found a 96% success rate for deployment/implantation but with a 7% incidence of serious complications.[126]​ Another nonpharmacologic approach to isolate and occlude LAA is to tie off the LAA using the LARIAT device, which is an epicardial snare.[127]​ The WATCHMAN FLX™ device is a next-generation LAA closure device that has a greater number of struts and dual-row J-shaped anchors to maximize device stability. A prospective, nonrandomized, multicenter study (PINNACLE FLX) found the WATCHMAN FLX™ to be associated with a low incidence of adverse events and a high incidence of anatomic closure.[128]

Concomitant surgical LAA exclusion may be considered (in addition to continued anticoagulation) in patients with a CHA₂DS₂-VASc score ≥2 or equivalent stroke risk who are undergoing cardiac surgery (e.g., coronary artery bypass graft or valve surgery).[1]

Plus – lifestyle and risk factor modification

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rate-control strategy selected
|
contraindications to long-term anticoagulation
Plus – 

lifestyle and risk factor modification

Treatment recommended for ALL patients in selected patient group

All patients with atrial fibrillation (AF) should receive comprehensive guideline-directed lifestyle and risk factor modification, which includes maintenance of ideal weight and weight loss if overweight or obese (the US guidelines recommend an ideal target weight of at least 10% weight loss); having a physically active lifestyle; reducing unhealthy alcohol consumption; stopping smoking; controlling diabetes; and controlling blood pressure/hypertension.[1]

Patients with AF should also have their risk factors for sleep-disordered breathing (SDB) considered, and screening, diagnosis, and management of SDB provided where indicated.[43]

paroxysmal or persistent AF and hemodynamically stable: rhythm-control strategy selected

1st line – direct current (DC) or pharmacologic cardioversion

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rhythm-control strategy selected
|
no contraindications to long-term anticoagulation
1st line – 

direct current (DC) or pharmacologic cardioversion

Either DC cardioversion or pharmacologic cardioversion can be considered in hemodynamically stable patients.[1] DC cardioversion is quicker and more effective than pharmacologic cardioversion and is generally preferred, but it requires sedation.

Both DC and pharmacologic cardioversion are associated with increased risk of thromboembolic events and risk must be minimized before going ahead.[147][148]​​​​ If cardioversion is indicated for an episode of AF ≥48 hours or of unknown duration, it must be performed only after a minimum of 3 weeks on oral anticoagulation (DOAC or warfarin), or after imaging to rule out presence of an intracardiac thrombus (e.g., if patient has had previous LAAO and is not receiving anticoagulation).[1] If the duration of AF is <48 hours, cardioversion is generally thought to have a low risk of thromboembolic events with anticoagulation afterward; however, imaging to rule out the presence of an intracardiac thrombus may be considered before cardioversion, particularly in those who have not received a minimum of 3 weeks on oral anticoagulation and those at higher thromboembolic risk.[1] The benefit of pericardioversion anticoagulation or imaging in patients with a low risk of thromboembolism and AF duration <12 hours is uncertain.[1] AF that is asymptomatic before the immediate event is common, making a determination of the duration uncertain. Guidelines recommend that therapeutic anticoagulation is started before cardioversion and continued for at least 4 weeks afterwards.[1] If intracardiac thrombus is identified on imaging and cardioversion is delayed, anticoagulation is given for a minimum of 3 to 6 weeks and imaging repeated before cardioversion is considered again.[1]

In patients with hemodynamically stable persistent AF with preserved left ventricular function and no evidence of metabolic and electrolyte disturbances, pharmacologic cardioversion may be attempted with administration of intravenous ibutilide under close telemetry monitoring.[1] Because the half-life of ibutilide is 3 to 6 hours, prolonged observation period is recommended in patients who have received ibutilide.[150][151]​​ Intravenous amiodarone is also an option for pharmacologic cardioversion (including patients with HF), but time to cardioversion is longer than with ibutilide.[1][2]

Pretreatment with antiarrhythmic drugs may be considered in some patients to facilitate the success of DC cardioversion and reduce risk of AF recurrence.[150][151]

If pharmacologic conversion is attempted and is unsuccessful, DC conversion should be considered rather than switching to an alternative antiarrhythmic agent.[1]

Selected outpatients who have recurrent AF may self-administer a single oral dose of flecainide or propafenone (known as the "pill-in-the-pocket" approach).[1][2]​​ An atrioventricular node-blocking agent (beta-blocker or nondihydropyridine calcium-channel blocker) should be administered concomitantly, to prevent atrial flutter with 1:1 conduction. Safety and efficacy of this approach in selected patients should be established first in a monitored hospital setting.[1][2]

Considerations for patients with comorbid HF: antiarrhythmic drugs should be used very cautiously especially in patients with abnormal LV function and HF. Some antiarrhythmic agents, such as sotalol, may increase mortality.[157]​ Ibutilide may be used for pharmacologic cardioversion in patients with HFpEF (EF >40%), but should be avoided in patients with HFrEF (EF ≤40%). Intravenous amiodarone is an option for both those with HFpEF and HFrEF (but time to cardioversion is longer than with ibutilide).[1][2]

Considerations for patients with comorbid CKD: there are limited data on management of AF in patients with CKD. Doses of antiarrhythmic drugs are adjusted based on pharmacokinetic data and clinical experience.[1]​ Some drugs should be used with caution in patients with renal impairment and a dose adjustment may be required. Some drugs may also be contraindicated in patients with renal impairment. Check your local drug information source for more information.

Considerations for patients with comorbid Wolff-Parkinson-White (WPW) syndrome: in patients with AF and WPW syndrome, rapid conduction of atrial electrical activity to the ventricles via an accessory pathway (preexcitation) may cause fast ventricular rates, with an increased risk of ventricular fibrillation and sudden death.[1][2]​​ Hemodynamically stable patients with preexcited AF may be treated with pharmacologic cardioversion. AV nodal blocking agents (e.g., verapamil, diltiazem, amiodarone, digoxin, adenosine, beta-blockers) are contraindicated in preexcited AF. Hemodynamically unstable patients with preexcited AF should be treated with DC cardioversion.

Considerations for patients with comorbid chronic coronary disease: class Ic agents (e.g., flecainide, propafenone) have a higher mortality in patients with coronary artery disease (CAD) and are contraindicated in patients with CAD and cardiac dysfunction.[1]

Considerations for patients with comorbid cancer: patients with AF and cancer should be managed by a multidisciplinary team. Treatments for AF may be less effective if it is caused directly by the cancer therapy.[59]​ Drug-drug interactions can occur between cancer therapies and AF therapies. When using antiarrhythmic agents, risk of QT interval prolongation should be considered as patients with cancer are already at an increased risk.[1]

Considerations for patients with comorbid ACHD: the US guidelines advise that adults with moderate or complex CHD may tolerate AF poorly and rhythm control is generally preferred over rate control. Choice of antiarrhythmic must be individualized.[1]

Considerations for patients with select comorbidities: a rhythm control strategy may be preferred in patients with comorbid hypertrophic cardiomyopathy or pulmonary disease.[1][185]

Primary options

ibutilide: body weight <60 kg: 0.01 mg/kg intravenously as a single dose; adults body weight ≥60 kg: 1 mg intravenously as a single dose; may repeat dose after 10 minutes if no response

OR

amiodarone: 150 mg intravenously initially over 10 minutes, followed by 1 mg/minute infusion for 6 hours, and then 0.5 mg/minute infusion for 18 hours; 600-800 mg/day orally given in 2-3 divided doses up to a total loading dose of up to 10 g, followed by 200 mg orally once daily

More

Secondary options

flecainide: body weight <70 kg: 200 mg orally as a single dose; body weight ≥70 kg: 300 mg orally as a single dose

More

OR

propafenone: body weight <70 kg: 450 mg orally as a single dose; body weight ≥70 kg: 600 mg orally as a single dose

More

Plus – estimate stroke risk and consider anticoagulation

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rhythm-control strategy selected
|
no contraindications to long-term anticoagulation
Plus – 

estimate stroke risk and consider anticoagulation

Treatment recommended for ALL patients in selected patient group

Risk of stroke and thromboembolic events should be assessed in all patients using a validated clinical risk score, such as the CHA₂DS₂-VASc tool.[1][2][78]​​​​ Guidelines from the American College of Cardiology/American Heart Association/American Association of Colleges of Pharmacy/Heart Rhythm Society (ACC/AHA/ACCP/HRS) recommend that the risk is evaluated annually.[1]

The CHA₂DS₂-VASc tool is the most validated risk score and is most widely used.[1][2][78]​​​​​​ CHA₂DS₂-VASc allocates 1 point each for chronic heart failure, hypertension, age 65 to 74 years, diabetes mellitus, vascular disease, and female sex, and 2 points each for a history of stroke or transient ischemic attack, or age 75 years and older.[99] [ Atrial Fibrillation CHA(2)DS(2)-VASc Score for Stroke Risk Opens in new window ] ​​​​ The ACC/AHA/ACCP/HRS and ESC guidelines recommend the use of oral anticoagulants for patients with AF and a CHA₂DS₂-VASc score of ≥2 in men or ≥3 in women (1 for gender, and 2 for additional risk factors), which corresponds to annual thromboembolic risk of ≥2%.[1][2]​​​​​​ With a score of ≥1 in men or ≥2 in women (1 for gender and 1 for additional risk factors; corresponds to annual risk of ≥1% to <2%), the use of oral anticoagulants to prevent thromboembolic stroke can be considered; additional factors that may modify stroke risk, such as hypertension control, can be taken into account.​[1][2]​​​​​​ Use of oral anticoagulants in patients with a nonsex-related CHA₂DS₂-VASc score of 1 is particularly important to consider in patients over the age of 65 years.[3]

Use of any anticoagulation strategy needs to be balanced with the risk of bleeding, particularly intracranial bleeding.[100] Scoring systems such as ORBIT, HAS-BLED, HEMORR₂HAGES, and the newer DOAC score can help to quantify this risk and assess how the bleeding risk can be minimized.[101] MdCalc. HEMORR₂HAGES Score for Major Bleeding Risk Opens in new window​​​​​​ [ ORBIT Bleeding Risk Score Opens in new window ] [ HAS-BLED Bleeding Risk Score Opens in new window ] ​​​​​​ When used in combination with a stroke risk score such as CHA₂DS₂-VASc, bleeding risk tools provide a means to balance the benefits and risks of anticoagulation with patients. Bleeding risk scores should not be used to exclude people from receiving anticoagulant treatment.[1][2][102]

In patients with cardiac implantable electronic devices, AF may be detected as AHRE, which can be silent/asymptomatic. Anticoagulation therapy for prevention of thromboembolism and stroke based on subclinical AF has not shown to be convincingly useful; use of DOACs in the ARTESIA and NOAH-AF trials was associated with increased risk of major bleeding.[103][104]​ In patients who have longer duration AHREs, are at higher risk of stroke (e.g., measured by CHA₂DS₂-VASc), and have symptomatic AF, anticoagulation may be of benefit.[1][2][105]

Oral anticoagulation drugs for stroke prevention are warfarin or a DOAC such as dabigatran, rivaroxaban, apixaban, or edoxaban. All patients should preferably be started on a DOAC, unless they are not eligible (e.g., presence of moderate to severe mitral valve stenosis or mechanical prosthetic valves) or DOACs are not available.[1][2]​​​[78]​​​​ DOACs are generally safe in older patients; however, dabigatran may be associated with an increased risk of gastrointestinal bleeding compared with warfarin.[117]

If DOACs are used in patients with renal impairment they should be used with caution. Some DOACs may require dose adjustment and some may be contraindicated. Consult a drug information source for specific guidance on use in patients with renal impairment. DOACs should not be used in combination with heparin (including LMWH), heparin derivatives, or warfarin.

The efficacy and safety of anticoagulation with warfarin is highly dependent on the quality of anticoagulation control as reflected by the average time in therapeutic range (TTR) of INR 2 to 3. The SAMe-TT₂R₂ scoring system (based on sex, age, medical history, treatment interactions, tobacco use, and race) is a tool that may help identify anticoagulation-naive patients who are less likely to maintain TTR >70% and who should, therefore, be managed with DOACs instead of warfarin.[118][119] SAMe-TT₂R₂ score Opens in new window​​​​​​​​

Recommendations for anticoagulation in patients with concomitant conditions are available and should be consulted.[1][2]​​​​

Concomitant surgical LAA exclusion may be considered (in addition to continued anticoagulation) in patients with a CHA₂DS₂-VASc score ≥2 or equivalent stroke risk who are undergoing cardiac surgery (e.g., coronary artery bypass graft or valve surgery).[1]

The ACC/AHA/ACCP/HRS, ESC, and NICE (UK) guidelines do not recommend aspirin as an alternative to anticoagulation for stroke prevention in patients with AF.[1][2][78]

Considerations for patients with comorbid obesity: DOACs may be used over warfarin in those with class III obesity (BMI ≥40 kg/m²). Warfarin may be preferred in those who have undergone bariatric surgery.[1]

Considerations for patients with comorbid diabetes: DOACs are associated with reduced vascular mortality compared with warfarin in those with AF and diabetes.[1][2]

Considerations for patients with comorbid VHD: the US guidelines recommend that patients with AF and significant (moderate or greater) mitral stenosis or a mechanical heart valve should receive long-term anticoagulation regardless of CHA₂DS₂-VASc score.[1]​ Warfarin is recommended over DOACs in these patients.[1][2]​ In patients with AF and other comorbid VHD (i.e., not moderate-to-severe mitral stenosis or a mechanical heart valve), DOACs may be used over warfarin.[1][2]

Considerations for patients with comorbid CKD: renal function must be considered when selecting an anticoagulant regimen. Some drugs should be used with caution in patients with renal impairment and a dose adjustment may be required. Some drugs may also be contraindicated in patients with renal impairment. Check your local drug information source for more information. The US guidelines advise that patients with stage 3 CKD may receive either a DOAC (preferred) or warfarin; patients with stage 4 CKD may reasonably receive either warfarin or a DOAC; and patients with end-stage CKD (CrCl <15 mL/min) or who are on dialysis may reasonably receive warfarin or apixaban.[1]​ In Europe, DOACs are not approved for patients with CrCl ≤15 mL/min or on dialysis.[2]

Considerations for patients with comorbid liver disease: in those with mild or moderate liver disease (Child-Pugh score A or B), DOACs may be used over warfarin; however, rivaroxaban should not be used in moderate liver disease (Child-Pugh B).[1][2]​ There are no data on use of DOACs in patients with severe liver disease (Child-Pugh class C). In Europe, DOACs are contraindicated in these patients.[1][2]​ Warfarin may be used in patients with Child-Pugh class C liver disease; in high-risk patients (recent major bleeding, active coagulopathy, severe thrombocytopenia, or high-risk varices not amenable to intervention) decision to use is individualized.[184]

Considerations for patients with comorbid HCM: patients with HCM and AF should receive long-term anticoagulation regardless of CHA₂DS₂-VASc score.[1]​ The US guidelines recommend DOACs as the preferred option in patients with HCM and AF, and warfarin as the second-line alternative.[185]

Considerations for patients with comorbid cancer: patients with AF and cancer should be managed by a multidisciplinary team. When choosing an anticoagulant in patients with cancer and AF, the cancer type, status, and prognosis, as well as the patient’s bleeding/thromboembolic risk should all be considered. DOACs are recommended as first-line in patients without a high bleeding risk, severe renal dysfunction, or significant drug-drug interactions. LMWH (not detailed here) can be considered in patients who have active cancer and AF but are not suitable for DOACs.[59]

ACHD: Some patients with moderate or complex CHD (e.g., Fontan circulation, cyanosis) are at higher risk for thromboembolic events and anticoagulation may be indicated regardless of usual AF risk score.[1][2]

Primary options

dabigatran etexilate: 150 mg orally twice daily

OR

apixaban: 2.5 to 5 mg orally twice daily

OR

edoxaban: 60 mg orally once daily

OR

rivaroxaban: 20 mg orally once daily

OR

warfarin: 2-5 mg orally once daily initially, adjust dose according to target INR

More

Plus – lifestyle and risk factor modification

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rhythm-control strategy selected
|
no contraindications to long-term anticoagulation
Plus – 

lifestyle and risk factor modification

Treatment recommended for ALL patients in selected patient group

All patients with atrial fibrillation (AF) should receive comprehensive guideline-directed lifestyle and risk factor modification, which includes maintenance of ideal weight and weight loss if overweight or obese (the US guidelines recommend an ideal target weight of at least 10% weight loss); having a physically active lifestyle; reducing unhealthy alcohol consumption; stopping smoking; controlling diabetes; and controlling blood pressure/hypertension.[1]

Patients with AF should also have their risk factors for sleep-disordered breathing (SDB) considered, and screening, diagnosis, and management of SDB provided where indicated.[43]

Consider – catheter or surgical ablation

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rhythm-control strategy selected
|
no contraindications to long-term anticoagulation
Consider – 

catheter or surgical ablation

Treatment recommended for SOME patients in selected patient group

Catheter ablation may be used as a first-line option in some patients and in other patients is used when antiarrhythmic drugs have been ineffective, not tolerated, or are contraindicated.[1][2][158]​​​​​

Isolation of the pulmonary vein is generally recommended as the target of ablation, unless another specific AF trigger is identified.[1][2][158]​​​​ Catheter ablation using either radiofrequency or cryo energy to create pulmonary vein isolation (PVI) results in similar outcomes.[158]​​[159][160]​​ Additional complex atrial substrate modification ablation strategies (e.g., linear ablations to isolate the roof and the posterior wall of the left atrium, ablation of complex fractionated atrial electrograms, focal source, or rotors) may be considered, but the benefit of this versus PVI alone is not confirmed.[1][2][158]​​

Randomized controlled trials have demonstrated the superiority of catheter ablation over drug therapy for rhythm control in select patients.[161][162][163][164][165][166]​​ 

Patients with persistent AF who are in AF at the time of ablation should have a TEE performed to screen for thrombus. Risk of thromboembolic events is increased following catheter ablation and all patients should receive uninterrupted oral anticoagulation before, during, and after ablation.[1][158]​​​​ Following ablation therapy, anticoagulation is continued for at least 3 months, or longer depending on underlying risk factors (such as stroke risk). Rate-lowering medications and antiarrhythmics may also be continued, but this will depend on various patient factors, and the decision is individualized. If symptomatic AF recurs after catheter ablation, a repeat procedure often results in a better success rate.

Surgical ablation (open surgery, rather than using catheter techniques) is most often reserved for those who are having cardiac surgery for other reasons, such as bypass or valve surgery (e.g., mitral-valve surgery). It may also be used in patients with left atrial thrombus, or it may be chosen by certain patients who do not prefer the catheter approach, in which case a minimally invasive surgical approach is often used.[158]​​[176]​​ The Cox maze procedure is the conventional surgical approach. Multiple, precisely placed incisions are made in both atria, with the aim of isolating and terminating the abnormal electrical impulses' routes. The Cox maze IV procedure uses a modified approach.[177][178]​​ Alternative methods of creating lesions in the atria by ablation rather than incision have also been developed (e.g., radiofrequency, microwave, cryotherapy, and ultrasound). Hybrid convergent ablation, which combines minimally invasive surgical (epicardial) and catheter (endocardial) ablation, may be considered for patients with symptomatic, persistent AF refractory to antiarrhythmic drug therapy.[1][2][179]​​​​

Considerations for patients with comorbid HF: patients with AF and HF more likely to benefit from catheter ablation are generally younger, have an earlier stage of HF, and have less severe disease.[174][175]​ In patients with HFrEF(EF ≤40%) factors that should be taken into account include LV dysfunction, functional class, comorbid conditions, hemodynamic stability, ventricular scar burden, duration of AF, and degree of adverse atrial remodeling. Catheter ablation has been shown to improve outcomes compared with pharmacologic therapy/conventional treatment in patients with HF and AF.[166][167]

Considerations for patients with comorbid CKD: when performing catheter ablation in patients with CKD, particular attention must be paid to fluid balance when using irrigated radiofrequency catheters.[1]

Considerations for patients with comorbid HCM: a rhythm control strategy may be preferred in patients with HCM; choice of rhythm control is individualized. Catheter ablation may be considered, but is less effective in those with HCM compared with those without. Surgical ablation may also be considered as a potential rhythm management option in patients undergoing surgical myectomy.[185]

Considerations for patients with comorbid ACHD: the US guidelines advise that adults with moderate or complex CHD may tolerate AF poorly and rhythm control is generally preferred over rate control. Ablation may be an option in patients with AF and simple CHD. Electrophysiologic procedures should be performed by those with expertize in ACHD and in collaboration with an ACHD cardiologist.[1]

Consider – pharmacologic maintenance of sinus rhythm

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rhythm-control strategy selected
|
no contraindications to long-term anticoagulation
Consider – 

pharmacologic maintenance of sinus rhythm

Treatment recommended for SOME patients in selected patient group

​Long-term use of antiarrhythmic drugs is considered for maintenance of sinus rhythm after cardioversion in patients in whom catheter ablation is not suitable or not preferred. Pharmacologic maintenance of sinus rhythm can also be considered while awaiting ablation.

Adverse effects associated with use of antiarrhythmics include bradycardia or worsening of underlying sinus node dysfunction, or AV block. There is a risk of other arrhythmias developing with the use of these antiarrhythmics for AF. Choice of antiarrhythmic agent is therefore primarily guided by safety, considering cardiac comorbidities and other risk factors for proarrhythmic events.[1][2] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ]

In patients with normal LV function, no previous myocardial infarction (MI), and no significant structural heart disease, dofetilide, dronedarone, flecainide, or propafenone are recommended.[1][2]​​ Amiodarone is an alternative option in these patients, but it is associated with a range of adverse effects and drug interactions, so is recommended only when other antiarrhythmics are ineffective or contraindicated. Sotalol may also be considered in this group.[1]

Although (like sotalol, propafenone, and flecainide) dronedarone is less effective than amiodarone for the maintenance of sinus rhythm, it has fewer adverse effects.[152][153][154][155]​​ Dronedarone is indicated to reduce the risk of hospitalization in patients with paroxysmal or persistent AF and associated cardiovascular risk factors (i.e., age >70 years, hypertension, diabetes mellitus, prior cerebrovascular accident, left atrial diameter ≥50 mm, or left ventricular ejection fraction <40%), who are in sinus rhythm, or who will be cardioverted.

Specific adverse effects are more associated with certain antiarrhythmic agents. For example, with class Ic agents (i.e., propafenone or flecainide), conversion of AF to atrial flutter can occur with a faster ventricular response. This is due to slowing of the atrial cycle length allowing faster AV nodal conduction. Indeed, patients can present with a wide complex tachycardia simulating ventricular tachycardia due to rate-dependent conduction slowing in the ventricular myocardium or a bundle-branch block pattern. Therefore, patients eligible for the use of class Ic antiarrhythmics (i.e., propafenone or flecainide) should always be taking an AV nodal blocking drug (e.g., beta-blocker, nondihydropyridine calcium-channel blocker) before initiating treatment.

Dofetilide and sotalol may cause QT prolongation and torsades de pointes. These agents should be initiated within the hospital cautiously under close telemetry monitoring, and dosing should be modified based on creatinine clearance.

It is important to monitor liver enzymes when patients are treated with dronedarone and amiodarone. For the latter, patients should also have at least 6-monthly assessment of thyroid function and annual assessment of pulmonary function tests, including diffusing lung capacity for carbon monoxide.[1]

Overall, antiarrhythmic drugs should be used very cautiously, especially in patients with abnormal left ventricular (LV) function and heart failure, as they may increase adverse events. Some antiarrhythmic agents such as sotalol may increase mortality.[157]

Considerations for patients with comorbid HF: in patients with AF and significant structural heart disease, including HFrEF, options for long-term maintenance of sinus rhythm are amiodarone or dofetilide.[1][2]​ Dronedarone may be considered in patients who do not have New York Heart Association (NYHA) class III-IV HF or decompensation in the last 4 weeks.[154]​ Sotalol should not be used in patients with HFrEF.[1][2]​ The ESC guidelines recommend amiodarone and dronedarone for long-term maintenance of sinus rhythm in patients with HFpEF, with sotalol as an alternative.[2]​ For patients with HFpEF and AF, the use of flecainide or propafenone is reasonable for long-term maintenance of sinus rhythm provided no previous MI, or known or suspected significant structural heart disease, or ventricular scar or fibrosis is present.[1]

Considerations for patients with comorbid VHD: the ESC guidelines recommend amiodarone and dronedarone for long-term maintenance of sinus rhythm in patients with AF and significant valvular disease, with sotalol as an alternative.[2]

Considerations for patients with comorbid CKD: there are limited data on management of AF in patients with CKD. Doses of antiarrhythmic drugs are adjusted based on pharmacokinetic data and clinical experience.[1]​ Some drugs should be used with caution in patients with renal impairment and a dose adjustment may be required. Some drugs may also be contraindicated in patients with renal impairment. Check your local drug information source for more information.

Considerations for patients with comorbid chronic coronary disease: for maintenance of sinus rhythm in patients with AF and CAD, the ESC guidelines recommend amiodarone and dronedarone, with sotalol as an alternative.[2]​ Class Ic agents (e.g., flecainide, propafenone) have a higher mortality in patients with CAD and are contraindicated in patients with CAD and cardiac dysfunction.[1]

Considerations for patients with comorbid cancer: patients with AF and cancer should be managed by a multidisciplinary team. Treatments for AF may be less effective if it is caused directly by the cancer therapy.[59]​ Drug-drug interactions can occur between cancer therapies and AF therapies. When using antiarrhythmic agents, risk of QT interval prolongation should be considered as patients with cancer are already at an increased risk.[1]

Considerations for patients with comorbid ACHD: the US guidelines advise that adults with moderate or complex CHD may tolerate AF poorly and rhythm control is generally preferred over rate control. Choice of antiarrhythmic must be individualized.[1]

Primary options

dofetilide: 500 micrograms orally twice daily initially, adjust dose according to QTc interval and creatinine clearance

More

OR

dronedarone: 400 mg orally twice daily

OR

flecainide: 50-300 mg/day orally given in 2-3 divided doses

More

OR

propafenone: 150-300 mg orally (immediate-release) three times daily; 225-425 mg orally (extended-release) twice daily

Secondary options

amiodarone: 400-800 mg/day orally given in 2-4 divided doses for 1-4 weeks (total loading dose 6-10 g), followed by 200 mg once daily

OR

sotalol: 40-80 mg orally twice daily initially for 3 days, followed by 80-160 mg twice daily

Consider – AV nodal blocking drug

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rhythm-control strategy selected
|
no contraindications to long-term anticoagulation
Consider – 

AV nodal blocking drug

Treatment recommended for SOME patients in selected patient group

Patients who are eligible for the use of class Ic antiarrhythmics (i.e., propafenone or flecainide) should always be taking an AV nodal blocking drug (e.g., beta-blocker, nondihydropyridine calcium-channel blocker) before initiating treatment.

Considerations for patients with comorbid WPW syndrome: AV nodal blocking drugs are contraindicated in preexcited AF.

Primary options

metoprolol tartrate: 25-200 mg orally (immediate-release) twice daily

OR

propranolol hydrochloride: 10-40 mg orally (immediate-release) three to four times daily

OR

atenolol: : 25-100 mg orally once daily

OR

nadolol: 10-240 mg orally once daily

OR

bisoprolol: 2.5 to 10 mg orally once daily

OR

carvedilol: 3.125 to 25 mg orally twice daily

OR

diltiazem: 120-360 mg orally (extended-release) once daily

OR

verapamil: 180-480 mg orally (extended-release) once daily

1st line – direct current (DC) or pharmacologic cardioversion

Back
ONGOING
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paroxysmal or persistent AF and hemodynamically stable: rhythm-control strategy selected
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contraindications to long-term anticoagulation
1st line – 

direct current (DC) or pharmacologic cardioversion

Either DC cardioversion or pharmacologic cardioversion can be considered in hemodynamically stable patients.[1] DC cardioversion is quicker and more effective than pharmacologic cardioversion and is generally preferred, but it requires sedation.

Both DC and pharmacologic cardioversion are associated with increased risk of thromboembolic events and risk must be minimized before going ahead.[147][148]​​​​​ If cardioversion is indicated for an episode of AF ≥48 hours or of unknown duration, it must be performed only after a minimum of 3 weeks on oral anticoagulation (DOAC or warfarin), or after imaging to rule out presence of an intracardiac thrombus (e.g., if patient has had previous LAAO and is not receiving anticoagulation).[1] If the duration of AF is <48 hours, cardioversion is generally thought to have a low risk of thromboembolic events with anticoagulation afterward; however, imaging to rule out the presence of an intracardiac thrombus may be considered before cardioversion, particularly in those who have not received a minimum of 3 weeks on oral anticoagulation and those at higher thromboembolic risk.[1] The benefit of pericardioversion anticoagulation or imaging in patients with a low risk of thromboembolism and AF duration <12 hours is uncertain.[1] AF that is asymptomatic before the immediate event is common, making a determination of the duration uncertain. Guidelines recommend that therapeutic anticoagulation is started before cardioversion and continued for at least 4 weeks afterwards.[1] If intracardiac thrombus is identified on imaging and cardioversion is delayed, anticoagulation is given for a minimum of 3 to 6 weeks and imaging repeated before cardioversion is considered again.[1]​ In those who have contraindication to long-term anticoagulants, either percutaneous or surgical left atrial occlusion/clipping/removal should be considered and recommended as the left atrial appendage is a major source for AF-related thrombus formation.

In patients with hemodynamically stable persistent AF with preserved left ventricular function and no evidence of metabolic and electrolyte disturbances, pharmacologic cardioversion may be attempted with administration of intravenous ibutilide under close telemetry monitoring.[1] Because the half-life of ibutilide is 3 to 6 hours, prolonged observation period is recommended in patients who have received ibutilide.[150][151]​​​​ Intravenous amiodarone is also an option for pharmacologic cardioversion (including patients with HF), but time to cardioversion is longer than with ibutilide.[1][2]

Pretreatment with antiarrhythmic drugs may be considered in some patients to facilitate the success of DC cardioversion and reduce risk of AF recurrence.[150][151]

If pharmacologic conversion is attempted and is unsuccessful, DC conversion should be considered rather than switching to an alternative antiarrhythmic agent.[1]

Selected outpatients who have recurrent AF may self-administer a single oral dose of flecainide or propafenone (known as the "pill-in-the-pocket" approach).[1][2]​​​ An atrioventricular node-blocking agent (beta-blocker or nondihydropyridine calcium-channel blocker) should be administered concomitantly, to prevent atrial flutter with 1:1 conduction. Safety and efficacy of this approach in selected patients should be established first in a monitored hospital setting.[1][2]

Considerations for patients with comorbid HF: antiarrhythmic drugs should be used very cautiously especially in patients with abnormal LV function and HF. Some antiarrhythmic agents, such as sotalol, may increase mortality.[157]​ Ibutilide may be used for pharmacologic cardioversion in patients with HFpEF (EF >40%), but should be avoided in patients with HFrEF (EF ≤40%). Intravenous amiodarone is an option for both those with HFpEF and HFrEF (but time to cardioversion is longer than with ibutilide).[1][2]

Considerations for patients with comorbid CKD: there are limited data on management of AF in patients with CKD. Doses of antiarrhythmic drugs are adjusted based on pharmacokinetic data and clinical experience.[1]​ Some drugs should be used with caution in patients with renal impairment and a dose adjustment may be required. Some drugs may also be contraindicated in patients with renal impairment. Check your local drug information source for more information.

Considerations for patients with comorbid WPW syndrome: in patients with AF and WPW syndrome, rapid conduction of atrial electrical activity to the ventricles via an accessory pathway (preexcitation) may cause fast ventricular rates, with an increased risk of ventricular fibrillation and sudden death.[1][2]​​ Hemodynamically stable patients with preexcited AF may be treated with pharmacologic cardioversion. AV nodal blocking agents (e.g., verapamil, diltiazem, amiodarone, digoxin, adenosine, beta-blockers) are contraindicated in preexcited AF. Hemodynamically unstable patients with preexcited AF should be treated with DC cardioversion.

Considerations for patients with comorbid chronic coronary disease: class Ic agents (e.g., flecainide, propafenone) have a higher mortality in patients with CAD and are contraindicated in patients with CAD and cardiac dysfunction.[1]

Considerations for patients with comorbid cancer: patients with AF and cancer should be managed by a multidisciplinary team. Treatments for AF may be less effective if it is caused directly by the cancer therapy.[59]​ Drug-drug interactions can occur between cancer therapies and AF therapies. When using antiarrhythmic agents, risk of QT interval prolongation should be considered as patients with cancer are already at an increased risk.[1]

Considerations for patients with comorbid ACHD: the US guidelines advise that adults with moderate or complex CHD may tolerate AF poorly and rhythm control is generally preferred over rate control. Choice of antiarrhythmic must be individualized.[1]

Considerations for patients with select comorbidities: a rhythm control strategy may be preferred in patients with comorbid hypertrophic cardiomyopathy or pulmonary disease.[1][185]

Primary options

ibutilide: body weight <60 kg: 0.01 mg/kg intravenously as a single dose; adults body weight ≥60 kg: 1 mg intravenously as a single dose; may repeat dose after 10 minutes if no response

OR

amiodarone: 150 mg intravenously initially over 10 minutes, followed by 1 mg/minute infusion for 6 hours, and then 0.5 mg/minute infusion for 18 hours; 600-800 mg/day orally given in 2-3 divided doses up to a total loading dose of up to 10 g, followed by 200 mg orally once daily

More

Secondary options

flecainide: body weight <70 kg: 200 mg orally as a single dose; body weight ≥70 kg: 300 mg orally as a single dose

More

OR

propafenone: body weight <70 kg: 450 mg orally as a single dose; body weight ≥70 kg: 600 mg orally as a single dose

More

Plus – estimate stroke risk and consider left atrial appendage occlusion

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rhythm-control strategy selected
|
contraindications to long-term anticoagulation
Plus – 

estimate stroke risk and consider left atrial appendage occlusion

Treatment recommended for ALL patients in selected patient group

​Risk of stroke and thromboembolic events should be assessed in all patients using a validated clinical risk score, such as the CHA₂DS₂-VASc tool.[1][2][78]

Left atrial appendage occlusion (LAAO) may be considered as an alternative for stroke prevention when there are absolute contraindications to use of anticoagulants, or the risk of bleeding outweighs the benefits.[1][2][78][123][124]​​ LAAO devices such as the WATCHMAN™ and the Amplatzer™ Cardiac Plug device may be implanted percutaneously via transeptal catheterization. In the PROTECT AF trial, the primary efficacy event rate (a composite end point of stroke, cardiovascular death, and systemic embolism) of the WATCHMAN™ device was considered noninferior to that of warfarin.[125]​ There was a higher rate of adverse safety events in the intervention group than in the control group due mainly to periprocedural complications. The Amplatzer™ Cardiac Plug consists of a small proximal disk, a central polyester patch, and a larger distal disk with hooks to anchor the device in the LAA. It does not require anticoagulation and a European trial found a 96% success rate for deployment/implantation but with a 7% incidence of serious complications.[126]​ Another nonpharmacologic approach to isolate and occlude LAA is to tie off the LAA using the LARIAT device, which is an epicardial snare.[127]​ The WATCHMAN FLX™ device is a next-generation LAA closure device that has a greater number of struts and dual-row J-shaped anchors to maximize device stability. A prospective, nonrandomized, multicenter study (PINNACLE FLX) found the WATCHMAN FLX™ to be associated with a low incidence of adverse events and a high incidence of anatomic closure.[128]

Concomitant surgical LAA exclusion may be considered (in addition to continued anticoagulation) in patients with a CHA₂DS₂-VASc score ≥2 or equivalent stroke risk who are undergoing cardiac surgery (e.g., coronary artery bypass graft or valve surgery).[1]

Plus – lifestyle and risk factor modification

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rhythm-control strategy selected
|
contraindications to long-term anticoagulation
Plus – 

lifestyle and risk factor modification

Treatment recommended for ALL patients in selected patient group

​All patients with atrial fibrillation (AF) should receive comprehensive guideline-directed lifestyle and risk factor modification, which includes maintenance of ideal weight and weight loss if overweight or obese (the US guidelines recommend an ideal target weight of at least 10% weight loss); having a physically active lifestyle; reducing unhealthy alcohol consumption; stopping smoking; controlling diabetes; and controlling blood pressure/hypertension.[1]

Patients with AF should also have their risk factors for sleep-disordered breathing (SDB) considered, and screening, diagnosis, and management of SDB provided where indicated.[43]

Consider – catheter or surgical ablation

Back
ONGOING
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paroxysmal or persistent AF and hemodynamically stable: rhythm-control strategy selected
|
contraindications to long-term anticoagulation
Consider – 

catheter or surgical ablation

Treatment recommended for SOME patients in selected patient group

​Catheter ablation may be used as a first-line option in some patients and in other patients is used when antiarrhythmic drugs have been ineffective, not tolerated, or are contraindicated.[1][2][158]​​​​​

Isolation of the pulmonary vein is generally recommended as the target of ablation, unless another specific AF trigger is identified.[1][2][158]​​​​ Catheter ablation using either radiofrequency or cryo energy to create pulmonary vein isolation (PVI) results in similar outcomes.[158]​​[159][160]​​ Additional complex atrial substrate modification ablation strategies (e.g., linear ablations to isolate the roof and the posterior wall of the left atrium, ablation of complex fractionated atrial electrograms, focal source, or rotors) may be considered, but the benefit of this versus PVI alone is not confirmed.[1][2]​​[158]​

Randomized controlled trials have demonstrated the superiority of catheter ablation over drug therapy for rhythm control in select patients.[161][162][163][164][165][166]​​ 

Patients with persistent AF who are in AF at the time of ablation should have a TEE performed to screen for thrombus. Risk of thromboembolic events is increased following catheter ablation and all patients should receive uninterrupted oral anticoagulation before, during, and after ablation.[1][158]​​​​ Following ablation therapy, anticoagulation is continued for at least 3 months, or longer depending on underlying risk factors (such as stroke risk). Rate-lowering medications and antiarrhythmics may also be continued, but this will depend on various patient factors, and the decision is individualized. If symptomatic AF recurs after catheter ablation, a repeat procedure often results in a better success rate.

Surgical ablation (open surgery, rather than using catheter techniques) is most often reserved for those who are having cardiac surgery for other reasons, such as bypass or valve surgery (e.g., mitral-valve surgery). It may also be used in patients with left atrial thrombus, or it may be chosen by certain patients who do not prefer the catheter approach, in which case a minimally invasive surgical approach is often used.[158]​​[176]​​ The Cox maze procedure is the conventional surgical approach. Multiple, precisely placed incisions are made in both atria, with the aim of isolating and terminating the abnormal electrical impulses' routes. The Cox maze IV procedure uses a modified approach.[177][178]​ Alternative methods of creating lesions in the atria by ablation rather than incision have also been developed (e.g., radiofrequency, microwave, cryotherapy, and ultrasound). Hybrid convergent ablation, which combines minimally invasive surgical (epicardial) and catheter (endocardial) ablation, may be considered for patients with symptomatic, persistent AF refractory to antiarrhythmic drug therapy.[1][2][179]

Considerations for patients with comorbid HF: patients with AF and HF more likely to benefit from catheter ablation are generally younger, have an earlier stage of HF, and have less severe disease.[174][175]​ In patients with HFrEF(EF ≤40%) factors that should be taken into account include LV dysfunction, functional class, comorbid conditions, hemodynamic stability, ventricular scar burden, duration of AF, and degree of adverse atrial remodeling. Catheter ablation has been shown to improve outcomes compared with pharmacologic therapy/conventional treatment in patients with HF and AF.[166][167]

Considerations for patients with comorbid CKD: when performing catheter ablation in patients with CKD, particular attention must be paid to fluid balance when using irrigated radiofrequency catheters.[1]

Considerations for patients with comorbid HCM: a rhythm control strategy may be preferred in patients with HCM; choice of rhythm control is individualized. Catheter ablation may be considered, but is less effective in those with HCM compared with those without. Surgical ablation may also be considered as a potential rhythm management option in patients undergoing surgical myectomy.[185]

Considerations for patients with comorbid ACHD: the US guidelines advise that adults with moderate or complex CHD may tolerate AF poorly and rhythm control is generally preferred over rate control. Ablation may be an option in patients with AF and simple CHD. Electrophysiologic procedures should be performed by those with expertize in ACHD and in collaboration with an ACHD cardiologist.[1]

Consider – pharmacologic maintenance of sinus rhythm

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rhythm-control strategy selected
|
contraindications to long-term anticoagulation
Consider – 

pharmacologic maintenance of sinus rhythm

Treatment recommended for SOME patients in selected patient group

Long-term use of antiarrhythmic drugs is considered for maintenance of sinus rhythm after cardioversion in patients in whom catheter ablation is not suitable or not preferred. Pharmacologic maintenance of sinus rhythm can also be considered while awaiting ablation.

Adverse effects associated with use of antiarrhythmics include bradycardia or worsening of underlying sinus node dysfunction, or AV block. There is a risk of other arrhythmias developing with the use of these antiarrhythmics for AF. Choice of antiarrhythmic agent is therefore primarily guided by safety, considering cardiac comorbidities and other risk factors for proarrhythmic events.[1][2] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ]

In patients with normal LV function, no previous myocardial infarction, and no significant structural heart disease, dofetilide, dronedarone, flecainide, or propafenone are recommended.[1][2]​​ Amiodarone is an alternative option in these patients, but it is associated with a range of adverse effects and drug interactions, so is recommended only when other antiarrhythmics are ineffective or contraindicated. Sotalol may also be considered in this group.[1]

Although (like sotalol, propafenone, and flecainide) dronedarone is less effective than amiodarone for the maintenance of sinus rhythm, it has fewer adverse effects.[152][153][154][155]​​ Dronedarone is indicated to reduce the risk of hospitalization in patients with paroxysmal or persistent AF and associated cardiovascular risk factors (i.e., age >70 years, hypertension, diabetes mellitus, prior cerebrovascular accident, left atrial diameter ≥50 mm, or left ventricular ejection fraction <40%), who are in sinus rhythm, or who will be cardioverted.

Specific adverse effects are more associated with certain antiarrhythmic agents. For example, with class Ic agents (i.e., propafenone or flecainide), conversion of AF to atrial flutter can occur with a faster ventricular response. This is due to slowing of the atrial cycle length allowing faster AV nodal conduction. Indeed, patients can present with a wide complex tachycardia simulating ventricular tachycardia due to rate-dependent conduction slowing in the ventricular myocardium or a bundle-branch block pattern. Therefore, patients eligible for the use of class Ic antiarrhythmics (i.e., propafenone or flecainide) should always be taking an AV nodal blocking drug (e.g., beta-blocker, diltiazem, or verapamil) before initiating treatment.

Dofetilide and sotalol may cause QT prolongation and torsades de pointes. These agents should be initiated within the hospital cautiously under close telemetry monitoring, and dosing should be modified based on creatinine clearance.

It is important to monitor liver enzymes when patients are treated with dronedarone and amiodarone. For the latter, patients should also have at least 6-monthly assessment of thyroid function and annual assessment of pulmonary function tests, including diffusing lung capacity for carbon monoxide.[1]

Overall, antiarrhythmic drugs should be used very cautiously, especially in patients with abnormal left ventricular (LV) function and heart failure, as they may increase adverse events. Some antiarrhythmic agents such as sotalol may increase mortality.[157]

Considerations for patients with comorbid HF: in patients with AF and significant structural heart disease, including HFrEF, options for long-term maintenance of sinus rhythm are amiodarone or dofetilide.[1][2]​ Dronedarone may be considered in patients who do not have New York Heart Association (NYHA) class III-IV HF or decompensation in the last 4 weeks.[154]​ Sotalol should not be used in patients with HFrEF.[1][2]​ The ESC guidelines recommend amiodarone and dronedarone for long-term maintenance of sinus rhythm in patients with HFpEF, with sotalol as an alternative.[2]​ For patients with HFpEF and AF, the use of flecainide or propafenone is reasonable for long-term maintenance of sinus rhythm provided no previous MI, or known or suspected significant structural heart disease, or ventricular scar or fibrosis is present.[1]

Considerations for patients with comorbid VHD: the ESC guidelines recommend amiodarone and dronedarone for long-term maintenance of sinus rhythm in patients with AF and significant valvular disease, with sotalol as an alternative.[2]

Considerations for patients with comorbid CKD: there are limited data on management of AF in patients with CKD. Doses of antiarrhythmic drugs are adjusted based on pharmacokinetic data and clinical experience.[1]​ Some drugs should be used with caution in patients with renal impairment and a dose adjustment may be required. Some drugs may also be contraindicated in patients with renal impairment. Check your local drug information source for more information.

Considerations for patients with comorbid chronic coronary disease: for maintenance of sinus rhythm in patients with AF and CAD, the ESC guidelines recommend amiodarone and dronedarone, with sotalol as an alternative.[2]​ Class Ic agents (e.g., flecainide, propafenone) have a higher mortality in patients with CAD and are contraindicated in patients with CAD and cardiac dysfunction.[1]

Considerations for patients with comorbid cancer: patients with AF and cancer should be managed by a multidisciplinary team. Treatments for AF may be less effective if it is caused directly by the cancer therapy.[59]​ Drug-drug interactions can occur between cancer therapies and AF therapies. When using antiarrhythmic agents, risk of QT interval prolongation should be considered as patients with cancer are already at an increased risk.[1]

Considerations for patients with comorbid ACHD: the US guidelines advise that adults with moderate or complex CHD may tolerate AF poorly and rhythm control is generally preferred over rate control. Choice of antiarrhythmic must be individualized.[1]

Primary options

dofetilide: 500 micrograms orally twice daily initially, adjust dose according to QTc interval and creatinine clearance

More

OR

dronedarone: 400 mg orally twice daily

OR

flecainide: 50-300 mg/day orally given in 2-3 divided doses

More

OR

propafenone: 150-300 mg orally (immediate-release) three times daily; 225-425 mg orally (extended-release) twice daily

Secondary options

amiodarone: 400-800 mg/day orally given in 2-4 divided doses for 1-4 weeks (total loading dose 6-10 g), followed by 200 mg once daily

OR

sotalol: 40-80 mg orally twice daily initially for 3 days, followed by 80-160 mg twice daily

Consider – AV nodal blocking drug

Back
ONGOING
|
paroxysmal or persistent AF and hemodynamically stable: rhythm-control strategy selected
|
contraindications to long-term anticoagulation
Consider – 

AV nodal blocking drug

Treatment recommended for SOME patients in selected patient group

Patients who are eligible for the use of class Ic antiarrhythmics (i.e., propafenone or flecainide) should always be taking an AV nodal blocking drug (e.g., beta-blocker, nondihydropyridine calcium-channel blocker) before initiating treatment.

Considerations for patients with comorbid WPW syndrome: AV nodal blocking drugs are contraindicated in preexcited AF.

Primary options

metoprolol tartrate: 25-200 mg orally (immediate-release) twice daily

OR

propranolol hydrochloride: 10-40 mg orally (immediate-release) three to four times daily

OR

atenolol: : 25-100 mg orally once daily

OR

nadolol: 10-240 mg orally once daily

OR

bisoprolol: 2.5 to 10 mg orally once daily

OR

carvedilol: 3.125 to 25 mg orally twice daily

OR

diltiazem: 120-360 mg orally (extended-release) once daily

OR

verapamil: 180-480 mg orally (extended-release) once daily

permanent AF

1st line – pharmacologic rate control

Back
ONGOING
|
permanent AF
|
no contraindications to long-term anticoagulation
1st line – 

pharmacologic rate control

In patients with permanent atrial fibrillation (AF) it is accepted, both by patients and physicians, that attempts at restoration of sinus rhythm would either be unsuccessful or detrimental. Therefore, a strategy of rate control is followed rather than rhythm control.

Beta-blockers and nondihydropyridine calcium-channel blockers (diltiazem or verapamil; if EF >40%) may be used for long-term rate control, with digoxin considered either alone or in combination if other options are not tolerated or contraindicated.[1][2]

Considerations for patients with comorbid HF: in patients with AF and HF with preserved EF (HFpEF; EF >40%), a beta-blocker or nondihydropyridine calcium-channel blocker is preferred for rate control. Nondihydropyridine calcium-channel blockers must not be used in patients with HF with reduced EF (HFrEF; EF ≤40%) owing to their negative inotropic effect. Digoxin is an alternative option for rate control in patients with AF and either HFpEF or HFrEF. The optimal target heart rate in patients with AF and HF is unclear.

Considerations for patients with comorbid pulmonary disease: cardioselective beta-blockers (e.g., atenolol, bisoprolol, metoprolol) may be used for rate control in patients with AF and COPD (other rate control agents may also be used, but beta-blockers do not need to be avoided). Beta-blockers should be avoided in patients with reactive airway disease, such as asthma.[1]

Considerations for patients with comorbid cancer: patients with AF and cancer should be managed by a multidisciplinary team. Treatments for AF may be less effective if it is caused directly by the cancer therapy.[59]​ Drug-drug interactions can occur between cancer therapies and AF therapies. Beta-blockers are preferred for rate control in patients with cancer and AF, particularly if the cancer therapies have potential cardiovascular risk; diltiazem and verapamil should be avoided due to associations with negative inotropic effects and drug-drug interactions.[59]

Primary options

metoprolol tartrate: 25-200 mg orally (immediate-release) twice daily

OR

propranolol hydrochloride: 10-40 mg orally (immediate-release) three to four times daily

OR

atenolol: : 25-100 mg orally once daily

OR

nadolol: 10-240 mg orally once daily

OR

bisoprolol: 2.5 to 10 mg orally once daily

OR

carvedilol: 3.125 to 25 mg orally twice daily

OR

diltiazem: 120-360 mg orally (extended-release) once daily

OR

verapamil: 180-480 mg orally (extended-release) once daily

Secondary options

digoxin: 0.25 to 0.5 mg intravenously as a loading dose, followed by 0.25 mg every 6 hours (maximum 1.5 mg/24 hours), then 0.0625 to 0.25 mg orally once daily

Plus – estimate stroke risk and consider anticoagulation

Back
ONGOING
|
permanent AF
|
no contraindications to long-term anticoagulation
Plus – 

estimate stroke risk and consider anticoagulation

Treatment recommended for ALL patients in selected patient group

Risk of stroke and thromboembolic events should be assessed in all patients using a validated clinical risk score, such as the CHA₂DS₂-VASc tool.[1][2][78]​​​​​ Guidelines from the American College of Cardiology/American Heart Association/American Association of Colleges of Pharmacy/Heart Rhythm Society (ACC/AHA/ACCP/HRS) recommend that the risk is evaluated annually.[1]

The CHA₂DS₂-VASc tool is the most validated risk score and is most widely used.[1][2][78]​​​​​ CHA₂DS₂-VASc allocates 1 point each for chronic heart failure, hypertension, age 65 to 74 years, diabetes mellitus, vascular disease, and female sex, and 2 points each for a history of stroke or transient ischemic attack, or age 75 years and older.[99] [ Atrial Fibrillation CHA(2)DS(2)-VASc Score for Stroke Risk Opens in new window ] ​​​​ The ACC/AHA/ACCP/HRS and ESC guidelines recommend the use of oral anticoagulants for patients with AF and a CHA₂DS₂-VASc score of ≥2 in men or ≥3 in women (1 for gender, and 2 for additional risk factors), which corresponds to annual thromboembolic risk of ≥2%.[1][2]​​​​​ With a score of ≥1 in men or ≥2 in women (1 for gender and 1 for additional risk factors; corresponds to annual risk of ≥1% to <2%), the use of oral anticoagulants to prevent thromboembolic stroke can be considered; additional factors that may modify stroke risk, such as hypertension control, can be taken into account.[1][2]​​​​​ Use of oral anticoagulants in patients with a nonsex-related CHA₂DS₂-VASc score of 1 is particularly important to consider in patients over the age of 65 years.[3]

Use of any anticoagulation strategy needs to be balanced with the risk of bleeding, particularly intracranial bleeding.[100] Scoring systems such as ORBIT, HAS-BLED, HEMORR₂HAGES, and the newer DOAC score can help to quantify this risk and assess how the bleeding risk can be minimized.[101] MdCalc: HEMORR₂HAGES Score for Major Bleeding Risk​ Opens in new window​​​​​​​​​​​​ [ ORBIT Bleeding Risk Score Opens in new window ] [ HAS-BLED Bleeding Risk Score Opens in new window ] ​​​​​​​​​​​ When used in combination with a stroke risk score such as CHA₂DS₂-VASc, bleeding risk tools provide a means to balance the benefits and risks of anticoagulation with patients. Bleeding risk scores should not be used to exclude people from receiving anticoagulant treatment.[1][2][102]​​​​​​​​​

In patients with cardiac implantable electronic devices, AF may be detected as AHRE, which can be silent/asymptomatic. Anticoagulation therapy for prevention of thromboembolism and stroke based on subclinical AF has not shown to be convincingly useful; use of DOACs in the ARTESIA and NOAH-AF trials was associated with increased risk of major bleeding.[103][104]​​ In patients who have longer duration AHREs, are at higher risk of stroke (e.g., measured by CHA₂DS₂-VASc), and have symptomatic AF, anticoagulation may be of benefit.[1][2][105]

Oral anticoagulation drugs for stroke prevention are warfarin or a DOAC such as dabigatran, rivaroxaban, apixaban, or edoxaban. All patients should preferably be started on a DOAC, unless they are not eligible (e.g., presence of moderate to severe mitral valve stenosis or mechanical prosthetic valves) or DOACs are not available.[1][2][78]​ DOACs are generally safe in older patients; however, dabigatran may be associated with an increased risk of gastrointestinal bleeding compared with warfarin.[117]

If DOACs are used in patients with renal impairment, they should be used with caution. Some DOACs may need dose adjustment and some may be contraindicated. Consult a drug information source for specific guidance on use in patients with renal impairment. DOACs should not be used in combination with heparin (including LMWH), heparin derivatives, or warfarin.

The efficacy and safety of anticoagulation with warfarin is highly dependent on the quality of anticoagulation control as reflected by the average time in therapeutic range (TTR) of INR 2 to 3. The SAMe-TT₂R₂ scoring system (based on sex, age, medical history, treatment interactions, tobacco use, and race) is a tool that may help identify anticoagulation-naive patients who are less likely to maintain TTR >70% and who should, therefore, be managed with DOACs instead of warfarin.[118][119] SAMe-TT₂R₂ score Opens in new window​​​​​​​​​

Recommendations for anticoagulation in patients with concomitant conditions are available and should be consulted.[1][2]​​​​​

Concomitant surgical LAA exclusion may be considered (in addition to continued anticoagulation) in patients with a CHA₂DS₂-VASc score ≥2 or equivalent stroke risk who are undergoing cardiac surgery (e.g., coronary artery bypass graft or valve surgery).[1]

The ACC/AHA/ACCP/HRS, ESC, and NICE (UK) guidelines do not recommend aspirin as an alternative to anticoagulation for stroke prevention in patients with AF.[1][2][78]

Considerations for patients with comorbid obesity: DOACs may be used over warfarin in those with class III obesity (BMI ≥40 kg/m²). Warfarin may be preferred in those who have undergone bariatric surgery.[1]

Considerations for patients with comorbid diabetes: DOACs are associated with reduced vascular mortality compared with warfarin in those with AF and diabetes.[1][2]

Considerations for patients with comorbid VHD: the US guidelines recommend that patients with AF and significant (moderate or greater) mitral stenosis or a mechanical heart valve should receive long-term anticoagulation regardless of CHA₂DS₂-VASc score.[1]​ Warfarin is recommended over DOACs in these patients.[1][2]​ In patients with AF and other comorbid VHD (i.e., not moderate-to-severe mitral stenosis or a mechanical heart valve), DOACs may be used over warfarin.[1][2]

Considerations for patients with comorbid CKD: renal function must be considered when selecting an anticoagulant regimen. Some drugs should be used with caution in patients with renal impairment and a dose adjustment may be required. Some drugs may also be contraindicated in patients with renal impairment. Check your local drug information source for more information. The US guidelines advise that patients with stage 3 CKD may receive either a DOAC (preferred) or warfarin; patients with stage 4 CKD may reasonably receive either warfarin or a DOAC; and patients with end-stage CKD (CrCl <15 mL/min) or who are on dialysis may reasonably receive warfarin or apixaban.[1]​ In Europe, DOACs are not approved for patients with CrCl ≤15 mL/min or on dialysis.[2]

Considerations for patients with comorbid liver disease: in those with mild or moderate liver disease (Child-Pugh score A or B), DOACs may be used over warfarin; however, rivaroxaban should not be used in moderate liver disease (Child-Pugh B).[1][2]​ There are no data on use of DOACs in patients with severe liver disease (Child-Pugh class C). In Europe, DOACs are contraindicated in these patients.[1][2]​ Warfarin may be used in patients with Child-Pugh class C liver disease; in high-risk patients (recent major bleeding, active coagulopathy, severe thrombocytopenia, or high-risk varices not amenable to intervention) decision to use is individualized.[184]

Considerations for patients with comorbid HCM: patients with HCM and AF should receive long-term anticoagulation regardless of CHA₂DS₂-VASc score.[1]​ The US guidelines recommend DOACs as the preferred option in patients with HCM and AF, and warfarin as the second-line alternative.[185]

Considerations for patients with comorbid cancer: patients with AF and cancer should be managed by a multidisciplinary team. When choosing an anticoagulant in patients with cancer and AF, the cancer type, status, and prognosis, as well as the patient’s bleeding/thromboembolic risk should all be considered. DOACs are recommended as first-line in patients without a high bleeding risk, severe renal dysfunction, or significant drug-drug interactions. LMWH (not detailed here) can be considered in patients who have active cancer and AF but are not suitable for DOACs.[59]

Considerations for patients with comorbid ACHD: Some patients with moderate or complex CHD (e.g., Fontan circulation, cyanosis) are at higher risk for thromboembolic events and anticoagulation may be indicated regardless of usual AF risk score.[1][2]

Primary options

dabigatran etexilate: 150 mg orally twice daily

OR

apixaban: 2.5 to 5 mg orally twice daily

OR

edoxaban: 60 mg orally once daily

OR

rivaroxaban: 20 mg orally once daily

OR

warfarin: 2-5 mg orally once daily initially, adjust dose according to target INR

More

Plus – lifestyle and risk factor modification

Back
ONGOING
|
permanent AF
|
no contraindications to long-term anticoagulation
Plus – 

lifestyle and risk factor modification

Treatment recommended for ALL patients in selected patient group

All patients with atrial fibrillation (AF) should receive comprehensive guideline-directed lifestyle and risk factor modification, which includes maintenance of ideal weight and weight loss if overweight or obese (the US guidelines recommend an ideal target weight of at least 10% weight loss); having a physically active lifestyle; reducing unhealthy alcohol consumption; stopping smoking; controlling diabetes; and controlling blood pressure/hypertension.[1]

Patients with AF should also have their risk factors for sleep-disordered breathing (SDB) considered, and screening, diagnosis, and management of SDB provided where indicated.[43]

2nd line – atrioventricular node ablation (AVNA) and pacing

Back
ONGOING
|
permanent AF
|
no contraindications to long-term anticoagulation
2nd line – 

atrioventricular node ablation (AVNA) and pacing

AVNA and pacemaker implantation may be considered for rate control when rapid ventricular response is refractory to pharmacologic rate control.[1][2]

Plus – estimate stroke risk and consider anticoagulation

Back
ONGOING
|
permanent AF
|
no contraindications to long-term anticoagulation
Plus – 

estimate stroke risk and consider anticoagulation

Treatment recommended for ALL patients in selected patient group

Risk of stroke and thromboembolic events should be assessed in all patients using a validated clinical risk score, such as the CHA₂DS₂-VASc tool.[1][2][78]​​​​​ Guidelines from the American College of Cardiology/American Heart Association/American Association of Colleges of Pharmacy/Heart Rhythm Society (ACC/AHA/ACCP/HRS) recommend that the risk is evaluated annually.[1]

The CHA₂DS₂-VASc tool is the most validated risk score and is most widely used.[1][2][78]​​​​​ CHA₂DS₂-VASc allocates 1 point each for chronic heart failure, hypertension, age 65 to 74 years, diabetes mellitus, vascular disease, and female sex, and 2 points each for a history of stroke or transient ischemic attack, or age 75 years and older.[99] [ Atrial Fibrillation CHA(2)DS(2)-VASc Score for Stroke Risk Opens in new window ] ​​​​ The ACC/AHA/ACCP/HRS and ESC guidelines recommend the use of oral anticoagulants for patients with AF and a CHA₂DS₂-VASc score of ≥2 in men or ≥3 in women (1 for gender, and 2 for additional risk factors), which corresponds to annual thromboembolic risk of ≥2%.[1][2]​​​​​ With a score of ≥1 in men or ≥2 in women (1 for gender and 1 for additional risk factors; corresponds to annual risk of ≥1% to <2%), the use of oral anticoagulants to prevent thromboembolic stroke can be considered; additional factors that may modify stroke risk, such as hypertension control, can be taken into account.[1][2]​​​​​ Use of oral anticoagulants in patients with a nonsex-related CHA₂DS₂-VASc score of 1 is particularly important to consider in patients over the age of 65 years.[3]

Use of any anticoagulation strategy needs to be balanced with the risk of bleeding, particularly intracranial bleeding.[100] Scoring systems such as ORBIT, HAS-BLED, HEMORR₂HAGES, and the newer DOAC score can help to quantify this risk and assess how the bleeding risk can be minimized.[101] MdCalc: HEMORR₂HAGES Score for Major Bleeding Risk​ Opens in new window​​​​​​​​​​​​ [ ORBIT Bleeding Risk Score Opens in new window ] [ HAS-BLED Bleeding Risk Score Opens in new window ] ​​​​​​​​​​​ When used in combination with a stroke risk score such as CHA₂DS₂-VASc, bleeding risk tools provide a means to balance the benefits and risks of anticoagulation with patients. Bleeding risk scores should not be used to exclude people from receiving anticoagulant treatment.[1][2][102]​​​​​​​​​

In patients with cardiac implantable electronic devices, AF may be detected as AHRE, which can be silent/asymptomatic. Anticoagulation therapy for prevention of thromboembolism and stroke based on subclinical AF has not shown to be convincingly useful; use of DOACs in the ARTESIA and NOAH-AF trials was associated with increased risk of major bleeding.[103][104]​ ​In patients who have longer duration AHREs, are at higher risk of stroke (e.g., measured by CHA₂DS₂-VASc), and have symptomatic AF, anticoagulation may be of benefit.[1][2][105]

Oral anticoagulation drugs for stroke prevention are warfarin or a DOAC such as dabigatran, rivaroxaban, apixaban, or edoxaban. All patients should preferably be started on a DOAC, unless they are not eligible (e.g., presence of moderate to severe mitral valve stenosis or mechanical prosthetic valves) or DOACs are not available.[1][2][78]​ DOACs are generally safe in older patients; however, dabigatran may be associated with an increased risk of gastrointestinal bleeding compared with warfarin.[117]

If DOACs are used in patients with renal impairment, they should be used with caution. Some DOACs may need dose adjustment and some may be contraindicated. Consult a drug information source for specific guidance on use in patients with renal impairment. DOACs should not be used in combination with heparin (including LMWH), heparin derivatives, or warfarin.

The efficacy and safety of anticoagulation with warfarin is highly dependent on the quality of anticoagulation control as reflected by the average time in therapeutic range (TTR) of INR 2 to 3. The SAMe-TT₂R₂ scoring system (based on sex, age, medical history, treatment interactions, tobacco use, and race) is a tool that may help identify anticoagulation-naive patients who are less likely to maintain TTR >70% and who should, therefore, be managed with DOACs instead of warfarin.[118][119] SAMe-TT₂R₂ score Opens in new window

Recommendations for anticoagulation in patients with concomitant conditions are available and should be consulted.[1][2]​​​​​​

Concomitant surgical LAA exclusion may be considered (in addition to continued anticoagulation) in patients with a CHA₂DS₂-VASc score ≥2 or equivalent stroke risk who are undergoing cardiac surgery (e.g., coronary artery bypass graft or valve surgery).[1]

The ACC/AHA/ACCP/HRS, ESC, and NICE (UK) guidelines do not recommend aspirin as an alternative to anticoagulation for stroke prevention in patients with AF.[1][2][78]

Considerations for patients with comorbid obesity: DOACs may be used over warfarin in those with class III obesity (BMI ≥40 kg/m²). Warfarin may be preferred in those who have undergone bariatric surgery.[1]

Considerations for patients with comorbid diabetes: DOACs are associated with reduced vascular mortality compared with warfarin in those with AF and diabetes.[1][2]

Considerations for patients with comorbid VHD: the US guidelines recommend that patients with AF and significant (moderate or greater) mitral stenosis or a mechanical heart valve should receive long-term anticoagulation regardless of CHA₂DS₂-VASc score.[1]​ Warfarin is recommended over DOACs in these patients.[1][2]​ In patients with AF and other comorbid VHD (i.e., not moderate-to-severe mitral stenosis or a mechanical heart valve), DOACs may be used over warfarin.[1][2]

Considerations for patients with comorbid CKD: renal function must be considered when selecting an anticoagulant regimen. The US guidelines advise that patients with stage 3 CKD may receive either a DOAC (preferred) or warfarin; patients with stage 4 CKD may reasonably receive either warfarin or a DOAC; and patients with end-stage CKD (CrCl <15 mL/min) or who are on dialysis may reasonably receive warfarin or apixaban.[1]​ In Europe, DOACs are not approved for patients with CrCl ≤15 mL/min or on dialysis.[2]

Considerations for patients with comorbid liver disease: in those with mild or moderate liver disease (Child-Pugh score A or B), DOACs may be used over warfarin; however, rivaroxaban should not be used in moderate liver disease (Child-Pugh B).[1][2]​ There are no data on use of DOACs in patients with severe liver disease (Child-Pugh class C). In Europe, DOACs are contraindicated in these patients.[1][2]​ Warfarin may be used in patients with Child-Pugh class C liver disease; in high-risk patients (recent major bleeding, active coagulopathy, severe thrombocytopenia, or high-risk varices not amenable to intervention) decision to use is individualized.[184]

Considerations for patients with comorbid HCM: patients with HCM and AF should receive long-term anticoagulation regardless of CHA₂DS₂-VASc score.[1]​ The US guidelines recommend DOACs as the preferred option in patients with HCM and AF, and warfarin as the second-line alternative.[185]

Considerations for patients with comorbid cancer: patients with AF and cancer should be managed by a multidisciplinary team. When choosing an anticoagulant in patients with cancer and AF, the cancer type, status, and prognosis, as well as the patient’s bleeding/thromboembolic risk should all be considered. DOACs are recommended as first-line in patients without a high bleeding risk, severe renal dysfunction, or significant drug-drug interactions. LMWH (not detailed here) can be considered in patients who have active cancer and AF but are not suitable for DOACs.[59]

ACHD: Some patients with moderate or complex CHD (e.g., Fontan circulation, cyanosis) are at higher risk for thromboembolic events and anticoagulation may be indicated regardless of usual AF risk score.[1][2]​ 

Primary options

dabigatran etexilate: 150 mg orally twice daily

OR

apixaban: 2.5 to 5 mg orally twice daily

OR

edoxaban: 60 mg orally once daily

OR

rivaroxaban: 20 mg orally once daily

OR

warfarin: 2-5 mg orally once daily initially, adjust dose according to target INR

More

Plus – lifestyle and risk factor modification

Back
ONGOING
|
permanent AF
|
no contraindications to long-term anticoagulation
Plus – 

lifestyle and risk factor modification

Treatment recommended for ALL patients in selected patient group

All patients with atrial fibrillation (AF) should receive comprehensive guideline-directed lifestyle and risk factor modification, which includes maintenance of ideal weight and weight loss if overweight or obese (the US guidelines recommend an ideal target weight of at least 10% weight loss); having a physically active lifestyle; reducing unhealthy alcohol consumption; stopping smoking; controlling diabetes; and controlling blood pressure/hypertension.[1]

Patients with AF should also have their risk factors for sleep-disordered breathing (SDB) considered, and screening, diagnosis, and management of SDB provided where indicated.[43]

1st line – pharmacologic rate control

Back
ONGOING
|
permanent AF
|
contraindications to long-term anticoagulation
1st line – 

pharmacologic rate control

In patients with permanent atrial fibrillation (AF) it is accepted, both by patients and physicians, that attempts at restoration of sinus rhythm would either be unsuccessful or detrimental. Therefore, a strategy of rate control is followed rather than rhythm control.

Beta-blockers and nondihydropyridine calcium-channel blockers (diltiazem or verapamil; if EF >40%) may be used for long-term rate control, with digoxin considered either alone or in combination if other options are not tolerated or contraindicated.[1][2]

Considerations for patients with comorbid HF: in patients with AF and HF with preserved EF (HFpEF; EF >40%), a beta-blocker or nondihydropyridine calcium-channel blocker is preferred for rate control. Nondihydropyridine calcium-channel blockers must not be used in patients with HF with reduced EF (HFrEF; EF ≤40%) owing to their negative inotropic effect. Digoxin is an alternative option for rate control in patients with AF and either HFpEF or HFrEF. The optimal target heart rate in patients with AF and HF is unclear.

Considerations for patients with comorbid pulmonary disease: cardioselective beta-blockers (e.g., atenolol, bisoprolol, metoprolol) may be used for rate control in patients with AF and COPD (other rate control agents may also be used, but beta-blockers do not need to be avoided). Beta-blockers should be avoided in patients with reactive airway disease, such as asthma.[1]

Considerations for patients with comorbid cancer: patients with AF and cancer should be managed by a multidisciplinary team. Treatments for AF may be less effective if it is caused directly by the cancer therapy.[59]​ Drug-drug interactions can occur between cancer therapies and AF therapies. Beta-blockers are preferred for rate control in patients with cancer and AF, particularly if the cancer therapies have potential cardiovascular risk; diltiazem and verapamil should be avoided due to associations with negative inotropic effects and drug-drug interactions.[59]

Primary options

metoprolol tartrate: 25-200 mg orally (immediate-release) twice daily

OR

propranolol hydrochloride: 10-40 mg orally (immediate-release) three to four times daily

OR

atenolol: : 25-100 mg orally once daily

OR

nadolol: 10-240 mg orally once daily

OR

bisoprolol: 2.5 to 10 mg orally once daily

OR

carvedilol: 3.125 to 25 mg orally twice daily

OR

diltiazem: 120-360 mg orally (extended-release) once daily

OR

verapamil: 180-480 mg orally (extended-release) once daily

Secondary options

digoxin: 0.25 to 0.5 mg intravenously as a loading dose, followed by 0.25 mg every 6 hours (maximum 1.5 mg/24 hours), then 0.0625 to 0.25 mg orally once daily

Plus – estimate stroke risk and consider left atrial appendage occlusion

Back
ONGOING
|
permanent AF
|
contraindications to long-term anticoagulation
Plus – 

estimate stroke risk and consider left atrial appendage occlusion

Treatment recommended for ALL patients in selected patient group

Risk of stroke and thromboembolic events should be assessed in all patients using a validated clinical risk score, such as the CHA₂DS₂-VASc tool.[1][2][78]

Left atrial appendage occlusion (LAAO) may be considered as an alternative for stroke prevention when there are absolute contraindications to use of anticoagulants, or the risk of bleeding outweighs the benefits.[1][2][78][123][124]​​​ LAAO devices such as the WATCHMAN™ and the Amplatzer™ Cardiac Plug device may be implanted percutaneously via transeptal catheterization. In the PROTECT AF trial, the primary efficacy event rate (a composite end point of stroke, cardiovascular death, and systemic embolism) of the WATCHMAN™ device was considered noninferior to that of warfarin.[125]​ There was a higher rate of adverse safety events in the intervention group than in the control group due mainly to periprocedural complications. The Amplatzer™ Cardiac Plug consists of a small proximal disk, a central polyester patch, and a larger distal disk with hooks to anchor the device in the LAA. It does not require anticoagulation and a European trial found a 96% success rate for deployment/implantation but with a 7% incidence of serious complications.[126]​ Another nonpharmacologic approach to isolate and occlude LAA is to tie off the LAA using the LARIAT device, which is an epicardial snare.[127]​ The WATCHMAN FLX™ device is a next-generation LAA closure device that has a greater number of struts and dual-row J-shaped anchors to maximize device stability. A prospective, nonrandomized, multicenter study (PINNACLE FLX) found the WATCHMAN FLX™ to be associated with a low incidence of adverse events and a high incidence of anatomic closure.[128]

Concomitant surgical LAA exclusion may be considered (in addition to continued anticoagulation) in patients with a CHA₂DS₂-VASc score ≥2 or equivalent stroke risk who are undergoing cardiac surgery (e.g., coronary artery bypass graft or valve surgery).[1]

Plus – lifestyle and risk factor modification

Back
ONGOING
|
permanent AF
|
contraindications to long-term anticoagulation
Plus – 

lifestyle and risk factor modification

Treatment recommended for ALL patients in selected patient group

All patients with atrial fibrillation (AF) should receive comprehensive guideline-directed lifestyle and risk factor modification, which includes maintenance of ideal weight and weight loss if overweight or obese (the US guidelines recommend an ideal target weight of at least 10% weight loss); having a physically active lifestyle; reducing unhealthy alcohol consumption; stopping smoking; controlling diabetes; and controlling blood pressure/hypertension.[1]

Patients with AF should also have their risk factors for sleep-disordered breathing (SDB) considered, and screening, diagnosis, and management of SDB provided where indicated.[43]

2nd line – atrioventricular node ablation (AVNA) and pacing

Back
ONGOING
|
permanent AF
|
contraindications to long-term anticoagulation
2nd line – 

atrioventricular node ablation (AVNA) and pacing

AVNA and pacemaker implantation may be considered for rate control when rapid ventricular response is refractory to pharmacologic rate control.[1][2]

Plus – estimate stroke risk and consider left atrial appendage occlusion

Back
ONGOING
|
permanent AF
|
contraindications to long-term anticoagulation
Plus – 

estimate stroke risk and consider left atrial appendage occlusion

Treatment recommended for ALL patients in selected patient group

Risk of stroke and thromboembolic events should be assessed in all patients using a validated clinical risk score, such as the CHA₂DS₂-VASc tool.[1][2][78]

Left atrial appendage occlusion (LAAO) may be considered as an alternative for stroke prevention when there are absolute contraindications to use of anticoagulants, or the risk of bleeding outweighs the benefits.[1][2][78][123][124]​​​ LAAO devices such as the WATCHMAN™ and the Amplatzer™ Cardiac Plug device may be implanted percutaneously via transeptal catheterization. In the PROTECT AF trial, the primary efficacy event rate (a composite end point of stroke, cardiovascular death, and systemic embolism) of the WATCHMAN™ device was considered noninferior to that of warfarin.[125]​ There was a higher rate of adverse safety events in the intervention group than in the control group due mainly to periprocedural complications. The Amplatzer™ Cardiac Plug consists of a small proximal disk, a central polyester patch, and a larger distal disk with hooks to anchor the device in the LAA. It does not require anticoagulation and a European trial found a 96% success rate for deployment/implantation but with a 7% incidence of serious complications.[126]​ Another nonpharmacologic approach to isolate and occlude LAA is to tie off the LAA using the LARIAT device, which is an epicardial snare.[127]​ The WATCHMAN FLX™ device is a next-generation LAA closure device that has a greater number of struts and dual-row J-shaped anchors to maximize device stability. A prospective, nonrandomized, multicenter study (PINNACLE FLX) found the WATCHMAN FLX™ to be associated with a low incidence of adverse events and a high incidence of anatomic closure.[128]

Concomitant surgical LAA exclusion may be considered (in addition to continued anticoagulation) in patients with a CHA₂DS₂-VASc score ≥2 or equivalent stroke risk who are undergoing cardiac surgery (e.g., coronary artery bypass graft or valve surgery).[1]

Plus – lifestyle and risk factor modification

Back
ONGOING
|
permanent AF
|
contraindications to long-term anticoagulation
Plus – 

lifestyle and risk factor modification

Treatment recommended for ALL patients in selected patient group

All patients with atrial fibrillation (AF) should receive comprehensive guideline-directed lifestyle and risk factor modification, which includes maintenance of ideal weight and weight loss if overweight or obese (the US guidelines recommend an ideal target weight of at least 10% weight loss); having a physically active lifestyle; reducing unhealthy alcohol consumption; stopping smoking; controlling diabetes; and controlling blood pressure/hypertension.[1]

Patients with AF should also have their risk factors for sleep-disordered breathing (SDB) considered, and screening, diagnosis, and management of SDB provided where indicated.[43]

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