- ACRONYMS
- ACC - American College of Cardiology
- ACCP - American College of Chest Physicians
- A fib - Atrial fibrillation
- AHA - American Heart Association
- ASA - Acetylsalicylic acid (aspirin)
- bpm - beats per minute
- CAD - Coronary Artery Disease
- CHF - Congestive heart failure
- DOAC - Direct-acting oral anticoagulant
- DVT - Deep vein thrombosis
- ECHO - short for Echocardiography. ECHO is an ultrasound of the heart that enables visualization of the anatomy and function of the heart.
- EF - Ejection fraction
- HFrEF - Heart failure with reduced ejection fraction
- INR - International normalized ratio
- PCI - Percutaneous coronary intervention (heart cath and associated procedures - stents, angioplasty, etc.)
- PE - Pulmonary embolism
- RCT - Randomized controlled trial
- TEE - TransEsophageal ECHO. Heart ECHO performed through the esophagus.
- TIA - Transient ischemic attack
- VKA - Vitamin K antagonist (e.g. warfarin)
- DEFINITIONS
- AV node (AtrioVentricular node) - bundle of specialized cells that conducts depolarization from the atria into the ventricles (see Illustration of cardiac conduction)
- Cryptogenic stroke - strokes that occur without an identifiable source of thrombosis or embolism. They are also referred to as "strokes of undetermined source." About 30% of strokes are considered cryptogenic.
- Depolarization - wave of positive charge initiated by the SA node that spreads through the atria and ventricles causing muscle contraction and a heartbeat
- Nonvalvular A fib - A fib that occurs in the absence of mitral valve disease or a prosthetic heart valve
- Paroxysmal A fib - A fib that comes on suddenly, continues for less than a week, and then reverts back to sinus rhythm spontaneously (AHA definition)
- Permanent A fib - A fib that lasts longer than 7 days and has failed to convert with cardioversion or cardioversion has not been attempted (AHA definition)
- Persistent A fib - A fib episodes that last longer than 7 days (AHA definition)
- Rapid ventricular rate - when the AV node transfers depolarizations from the atria to the ventricles at a rapid rate (> 100 bpm)
- SA node (SinoAtrial Node) - bundle of specialized cells that initiates depolarization of the atria. The SA node is the built-in pacemaker of the heart (see Illustration of cardiac conduction).
- Sinus rhythm - the normal heart rhythm
- PREVALENCE
- Atrial Fibrillation (A fib) is the most common heart arrhythmia, with an estimated prevalence of 0.4 - 1.0% in the general population. The risk of atrial fibrillation increases with age; the median age of diagnosis is 75 years, and 8% of people 80 years and older are believed to have the condition. [1]
- SCREENING
- Overview
- Atrial fibrillation can lead to strokes that cause significant morbidity and mortality. Symptoms of A fib vary widely, and many patients do not realize they have the condition; up to 30% of cryptogenic strokes are caused by undetected A fib. Because it can go unnoticed and effective treatments are available, there has been much interest in screening for the condition.
- Studies that have looked at the effects of A fib screening on long-term clinical outcomes have had mixed results. In one study, screening 75 - 76-year-olds with intermittent ECG for 2 weeks led to a slight decrease in a composite outcome of stroke, systemic embolism, bleeding leading to hospitalization, and all-cause death over 7 years (absolute risk reduction 1.1%, p=0.045). [PMID 34469764] Contrarily, a study that screened high-risk patients with an implantable loop recorder did not find a benefit of screening over 5.3 years. [PMID 34469766]
- Professional recommendations
- The USPSTF states that there is insufficient evidence to make a recommendation for or against A fib screening with ECG
- RISK FACTORS
- Age - most important
- Male sex
- Caucasians
- Heart Diseases
- Coronary artery disease
- Acute heart attack
- Pericarditis
- Myocarditis
- Cardiomyopathies
- Congestive heart failure
- Left ventricular hypertrophy
- Valvular heart disease (most often mitral valve)
- Hypertension
- Wolff-Parkinson-White syndrome
- Heavy alcohol intake (see alcohol reduction study below)
- Obesity
- Obstructive Sleep Apnea
- Genetic/familial
- Hyperthyroidism
- Fish oil
- Surgery (postoperative A fib)
- Electrocution
- Pulmonary embolism [1]
- Athletes [18]
- PHYSIOLOGY
- Arrhythmia
- Atrial Fibrillation is a heart arrhythmia marked by repetitive sporadic atrial depolarizations initiated from abnormal foci within the atrium. The abnormal electrical activity overrides the normal SA node, and the atria contract in an uncoordinated fashion. The AV node transmits the disorganized charges from the atria to the ventricles, causing an irregular rhythm. The heart rate in A fib can range from slow to fast, depending on how responsive the AV node is to the irregular discharges. Very rapid rates (>120 bpm) can hamper ventricular filling and lead to heart failure.
- Stroke
- The disorganized atrial activity caused by A fib can allow blood to pool and clot in the heart. The most common place for thrombus formation is the left atrial appendage (see atrial appendage), an outpocketing in the left atrium that is believed to be the source of > 90% of clots associated with A fib. If the clot breaks free, it can travel to the brain and cause a stroke. [10]
- DIAGNOSIS
- Symptoms
- A fib has a wide range of symptoms. Some people have no symptoms and are unaware that they have it, while others have overt heart failure. Some people are not aware they have A fib until they have a stroke.
- A fib can start suddenly and then revert back to sinus rhythm on its own. This is called paroxysmal or "sudden" A fib. A fib can also be persistent.
- Symptoms of A fib include:
- Palpitations
- Irregular heartbeat
- Heart failure in susceptible patients
- Chest pain in susceptible patients
- Stroke
- Physical exam
- Auscultation of the heart will typically reveal an irregular heartbeat consistent with A fib
- The pulse will also be irregular
- Signs of heart failure (pulmonary and lower extremity edema) may be present in susceptible individuals
- A fib can also occur after a pulmonary embolism
- Diagnostic workup
- The AHA recommends the following workup for A fib:
- ECG
- Transthoracic ECHO
- Labs for thyroid, kidney, and liver function
- In select cases, the following may be indicated:
- Holter monitor
- Transesophageal ECHO - if cardioversion is being considered
- Exercise testing - to evaluate adequacy of rate control
- Electrophysiological study - in patients who are considering ablation [1]
- Electrocardiogram (ECG)
- A fib can be diagnosed with an ECG. ECG findings consistent with A fib include wavy, nondistinct p-waves with ventricular depolarizations (QRS complexes) that occur at irregular intervals. If the ventricular response rate is rapid, only repetitive, nonuniformly-spaced QRS complexes may be present. See A fib ECG illustration for more.
- Cardiac monitoring
- Since A fib can come and go, the chance of detecting it increases the longer the heart rhythm is monitored. Detecting intermittent A fib is particularly important in patients who have had a stroke because it affects treatment recommendations. In a hospital or ER, heart rhythms can be monitored continuously with telemetry. For outpatient monitoring, a number of devices are now available for extended monitoring. A brief description of some of the more popular devices is given below.
- Holter monitor - external device with cardiac leads that can monitor the heart rhythm for up to 48 hours
- Zio® patch - small waterproof patch that provides a continuous reading for up to 2 weeks
- External loop recorder - device worn on the chest that performs a continuous ECG recording while the patient is wearing it. Most external loop recorders are worn for 4 - 6 weeks.
- Implantable loop recorder - small device implanted under the skin of the chest that can record and transmit heart rhythms for up to 3 years
- Smart watches - a number of smart watches now have the ability to detect A fib (e.g. Apple Watch, Fitbit)
- Heart echocardiogram (ECHO)
- A heart ECHO should be performed on all patients with newly-diagnosed A fib
- An ECHO can detect structural and functional abnormalities including heart valve diseases which are risk factors for A fib
- An ECHO can be performed in two ways - transthoracic and transesophageal
- A transthoracic ECHO is performed with a probe placed on the chest wall. A transesophageal echocardiogram (TEE) is performed with a probe that is run down the esophagus.
- The transesophageal ECHO (TEE) produces better images and allows better visualization of the left atrium and left atrial appendage where blood clots may be seen
- TEE may be preferred in patients who have suffered a stroke or in those who are to undergo cardioversion of their A fib. If TEE detects a clot then cardioversion should be delayed until anticoagulation has been achieved (see cardioversion recs below). [1]
- TREATMENT | Rate control
- Overview
- One issue in the treatment of A fib is whether to pursue a rate control or rhythm control strategy. In most stable patients, the AHA guidelines do not recommend one strategy over the other, but they do list factors that may favor a rhythm control strategy (see factors favoring rhythm control).
- Rate control is achieved with medications where rhythm control can be achieved with medications, cardioversion (electric and pharmacological), or catheter ablation
- Rate control in A fib involves slowing the rapid ventricular rate that the arrhythmia may produce. Several classes of medications are able to do this. The medications work by blocking the AV node which slows the conduction of depolarization from the atria to the ventricles (see cardiac conduction illustration).
- Medications used for rate control
- The RACE II study enrolled 614 patients with permanent atrial fibrillation
Main inclusion criteria
- Permanent A fib for 12 months
- Age ≤ 80 years
- Average resting heart rate > 80 bpm
- Current use of anticoagulation or aspirin
Baseline characteristics
- Average age 68 years
- Median duration of A fib - 18 months
- Previous cardioversion - 72%
- CAD - 18%
- Valvular heart disease - 20%
- CHADS2 score: 0 or 1 - 61% | 2 - 26% | 3 to 6 - 13%
- Average resting heart rate - 96
Randomized treatment groups
- Group 1 (311 patients) - Lenient rate control (target resting heart rate of < 110 bpm)
- Group 2 (303 patients) - Strict rate control (target resting heart rate of < 80 bpm, target heart rate of < 110 bpm during moderate exercise)
- Medications used to control heart rate were beta blockers, calcium channel blockers, and digoxin
Primary outcome: Composite of death from cardiovascular causes, hospitalization for heart failure, stroke, systemic embolism, major
bleeding, and arrhythmic events including syncope, sustained ventricular tachycardia, cardiac arrest, life-threatening adverse effects of rate-control drugs, and implantation of
a pacemaker or cardioverter–defibrillator
Results
Duration: 3 years | |||
Outcome | Lenient rate | Strict rate | Comparisons |
---|---|---|---|
Primary outcome | 12.9% | 14.9% | HR 0.84, 95%CI [0.58 - 1.21] |
Heart failure | 3.8% | 4.1% | HR 0.97, 95%CI [0.48 - 1.96] |
Stroke | 1.6% | 3.9% | HR 0.35, 95%CI [0.13 - 0.92] |
|
Findings: In patients with permanent atrial fibrillation, lenient rate control is as effective as strict rate control and is easier to achieve
- The AFFIRM study enrolled 4060 patients with atrial fibrillation
Main inclusion criteria
- Age ≥ 65 years
- A fib deemed to be recurrent and likely symptomatic
- Additional risk factors for stroke or death
Baseline characteristics
- Average age 70 years
- Hypertension - 51%
- CAD - 26%
- History of CHF - 23%
- Previously failed antiarrhythmic drug - 17.6%
Randomized treatment groups
- Group 1 (2027 patients) - Rate control only with beta blockers, calcium channel blockers, and/or digoxin. Target rate was ≤ 80 bpm resting and ≤ 110 bpm with six-minute walk test. Continuous anticoagulation with warfarin was mandated.
- Group 2 (2033 patients) - Rhythm control with common antiarrhythmic drugs. Cardioversion as needed. Anticoagulation with warfarin could be stopped if sinus rhythm was maintained for 4 - 12 weeks.
Primary outcome: Overall mortality
Results
Duration: Average of 3.5 years | |||
Outcome | Rate control | Rhythm control | Comparisons |
---|---|---|---|
Primary outcome | 25.9% | 26.7% | p=0.08 |
Stroke or brain bleed | 7.4% | 8.9% | p=0.93 |
Any hospitalization | 73% | 80% | p<0.001 |
|
Findings: Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy, and there are potential advantages,
such as a lower risk of adverse drug effects, with the rate-control strategy. Anticoagulation should be continued in this group of high-risk patients.
- The EAST-AFNET 4 trial enrolled 2789 patients with A fib diagnosed within the past 12 months
Main inclusion criteria
- Age ≥ 18 years
- A fib diagnosed within last 12 months
- Age > 75 years OR previous TIA/Stroke OR meet two of the following: age > 65 years, female sex, heart failure, hypertension, diabetes mellitus, severe CAD, chronic kidney disease (GFR 15 - 59 ml/min), LVH
Baseline characteristics
- Average age 70 years
- Previous stroke or TIA - 12%
- Stable heart failure - 29%
- Average CHA2DS2-VASc score - 3.4
- Median days since A fib diagnosis - 36
- Absence of A fib symptoms - 30%
- A fib type: First episode - 38% | Paroxysmal - 36% | Persistent - 26%
Randomized treatment groups
- Group 1 (1395 patients): Early rhythm control which consisted of antiarrhythmic drugs or ablation, as well as cardioversion of persistent atrial fibrillation soon after randomization
- Group 2 (1394 patients): Rate control therapy without rhythm control therapy. Rhythm control therapy was used only to mitigate uncontrolled atrial fibrillation–related symptoms during adequate rate control therapy.
- Treatment of cardiovascular conditions, anticoagulation, and rate control were mandated in all patients in accordance with guideline recommendations
Primary outcomes
- First: Composite of death from cardiovascular causes, stroke (either ischemic and hemorrhagic), or hospitalization with worsening of heart failure or acute coronary syndrome, analyzed in a time-to-event analysis
- Second: Number of nights spent in the hospital per year
Results
Duration: Median of 5.1 years | |||
Outcome | Rhythm control | Rate control | Comparisons |
---|---|---|---|
First primary outcome (%/year) | 3.9% | 5% | HR 0.79 (0.66 - 0.94) |
Secondary primary outcome (nights) | 5.8 | 5.1 | p=0.23 |
Stroke (%/year) | 0.6% | 0.9% | HR 0.65 (0.44 - 0.97) |
Death from CV causes (%/year) | 1.0% | 1.3% | HR 0.72 (0.52 - 0.98) |
Hospitalization for heart failure (%/year) | 2.1% | 2.6% | HR 0.81 (0.65 - 1.02) |
Hospitalization for coronary syndrome (%/year) | 0.8% | 1.0% | HR 0.83 (0.58 - 1.19) |
Overall mortality | 9.9% | 11.8% | N/A |
|
Findings: Early rhythm control therapy was associated with a lower risk of cardiovascular
outcomes than usual care among patients with early atrial fibrillation and cardiovascular conditions
- AHA recommendations
- The AHA recommends that beta blockers or nondihydropyridine calcium channel blockers be used first-line to control heart rate in A fib
- A heart rate control (resting heart rate < 80 bpm) strategy is reasonable for symptomatic management of A fib
- A lenient rate control strategy (resting heart rate < 110 bpm) may be reasonable with asymptomatic patients where left ventricular systolic function is preserved (see RACE II study)
- Nondihydropyridine calcium channel antagonists should not be used in decompensated heart failure
- Oral amiodarone may be useful for ventricular rate control when other measures are unsuccessful or contraindicated
- AV nodal ablation with permanent ventricular pacing is reasonable when pharmacological management is inadequate and rhythm control is not achievable
- When pre-excitation syndromes are present with A fib (see Wolff-Parkinson-White), digoxin, nondihydropyridine calcium channel antagonists, and amiodarone should not be administered [12]
- Summary
- In the RACE II Study, a lenient rate strategy (resting heart rate < 110 bpm) was as effective as a strict rate strategy (resting heart rate < 80 bpm)
- In the AFFIRM study, neither rhythm or rate control was shown to be superior to the other. The rhythm control group had significantly more hospitalizations and adverse events. The rhythm control group also had more than double the number of crossovers as the rate control group which speaks to the limited efficacy of antiarrhythmic medications
- In the EAST-AFNET 4 trial, an early rhythm control strategy that mainly used antiarrhythmic medications (86.8%) was slightly superior to a rate control strategy for a composite of CVD outcomes (absolute risk difference of 1.1%). The number needed to treat for 1 person to benefit from a rhythm control strategy is 91.
- TREATMENT | Rhythm control
- Overview
- All patients with A fib should be anticoagulated according to their individual risk factors (see stroke prevention below)
- The main treatment issue in A fib is typically whether to pursue a rate control or rhythm control strategy. In most stable patients, the AHA guidelines do not recommend one strategy over the other, but they do list factors that may favor a rhythm control strategy (see factors favoring rhythm control).
- Rhythm control in A fib involves converting the A fib arrhythmia back to sinus rhythm and preventing its recurrence
- There are three methods for achieving rhythm control: medications (pharmacological cardioversion), electrical cardioversion (heart shock), and catheter ablation
- Factors that may favor rhythm control over rate control
- Symptomatic A fib
- Difficulty in achieving adequate rate control
- Younger patient age
- Tachycardia-mediated cardiomyopathy
- First episode of A fib
- A fib that is precipitated by an acute illness
- Patient preference [13]
- Pharmacological cardioversion
- A number of antiarrhythmic medications can be used to convert A fib back into a sinus rhythm
- These medications are most effective when initiated in the first 7 days after the onset of A fib. A study that compared procainamide infusion to electrical cardioversion in patients presenting to the ER with acute A fib found that procainamide restored sinus rhythm in 52% of patients compared to 92% with cardioversion. [PMID 32007169]
- The medications can have serious side effects and are typically administered by cardiologists in a hospital setting. Some of them can also be used in an outpatient setting to maintain sinus rhythm in appropriate patients.
- Antiarrhythmic medications are able to maintain sinus rhythm in about 50% of patients who use them [4]
- See anticoagulation for cardioversion for recommendations on anticoagulant therapy before and after cardioversion
- Medications used to convert A fib and maintain sinus rhythm include:
- Amiodarone - convert A fib and maintain sinus rhythm
- Dofetilide- convert A fib and maintain sinus rhythm
- Dronedarone- maintain sinus rhythm
- Flecainide- convert A fib and maintain sinus rhythm
- Ibutilide- convert A fib
- Propafenone- convert A fib and maintain sinus rhythm
- Sotalol- maintain sinus rhythm [12]
- Electrical cardioversion
- Electrical cardioversion can be performed to convert A fib back into a sinus rhythm
- During the procedure, patients are sedated and an electrical shock is delivered to the heart
- The procedure may be necessary in patients who are unstable and need immediate conversion. It may also be performed as an elective outpatient procedure.
- Patients who present to the ER with new-onset A fib are often treated with attempted electrical cardioversion. A study in the NEJM (N=427) compared early vs delayed cardioversion in stable patients with A fib for < 36 hours who presented to an ER. The delayed group was given rate control medications and observed for 48 hours to see if the A fib would resolve, and the early group was cardioverted. In the delayed group, spontaneous conversion to sinus rhythm occurred in 69% of patients within 48 hours. The primary outcome of sinus rhythm at 4 weeks was not significantly different between groups (Early - 94% | Delayed - 91%). [PMID 30883054 ]
- See anticoagulation for cardioversion for recommendations on anticoagulant therapy before and after cardioversion
- Catheter ablation
- Procedure / Technique
- Cryoablation vs radiofrequency - Catheter ablation is a relatively new procedure where a probe is used to ablate tissue in the left atrium. The areas surrounding the entrance of the pulmonary veins are a frequent initiator of ectopic atrial foci, and ablating these tissues has been shown to reduce the occurrence of A fib. There are two ways to ablate the tissue; one method freezes the tissue (cryoablation), and the other uses radiofrequency energy. Several studies have compared the techniques and found them to be equivalent. [PMID 27042964, PMID 31630538]
- Left atrial fibrosis - left atrial fibrosisis is a hallmark of atrial myopathy and has been associated with a higher risk of A fib recurrence after ablation. Theoretically, ablating the fibrosis may lower the risk of recurrent A fib. A study (N=843) published in 2022 compared the effects of adding MRI-guided fibrosis ablation to standard ablation on atrial arrhythmia recurrence in patients with persistent A fib. There was no significant difference between the groups during the 12 - 18 month follow-up period. [PMID 35727277]
- Left atrial posterior wall isolation - persistent A fib is less responsive to ablation than paroxysmal A fib. Some experts have theorized that left atrial posterior wall conductive anomalies may be the reason, and adjunctive ablation of this area has risen in popularity. A study published in 2023 compared pulmonary vein isolation to pulmonary vein isolation + left atrial posterior wall isolation in symptomatic patients with persistent A fib. At 12 months post-ablation, no significant difference was found for the primary outcome of freedom from any documented atrial arrhythmia. [PMID 35727277]
- Vein of Marshall ablation - A small vein called the "Vein of Marshall" that runs along the left atrium and drains into the coronary sinus has been identified as another source of ectopic foci. A study that compared standard ablation to standard ablation + Vein of Marshall ablation (done with ethanol infusion) found that the addition of Vein of Marshall ablation improved success rates. [PMID 33107945]
- Periprocedural anticoagulants - Most patients continue taking their current anticoagulant when they have an ablation procedure done. Two studies have compared the safety of direct-acting oral anticoagulants (rivaroxaban and dabigatran) to warfarin for procedural anticoagulation. Both drugs were found to be equivalent to warfarin. [PMID 25975659, PMID 28317415]
- Ablate and pace - In patients with severely symptomatic A fib, an approach called "ablate and pace" is sometimes performed. Ablate and pace involves ablating the AV node and then pacing the ventricles with a biventricular pacemaker. A small study (N=133) found that this approach was superior to pharmacological rate control in patients with severe A fib and heart failure. [PMID 34453840]
- Efficacy (atrial fibrillation prevention)
- Depending on the study and the method used to detect A fib, catheter ablation has a success rate of about 57 - 70% for preventing recurrent A fib at one year post-ablation. At 2 years, success (defined as no atrial arrhythmia) has dropped to less than 50% in some trials. Repeat ablation is necessary in about 12 - 20% of patients. [4,9,11,17]
- A trial that compared initial treatment with cryoablation to antiarrhythmics is detailed below (EARLY-AF trial). The trial found that ablation was superior to antiarrhythmics for preventing A fib reoccurrence at 1 year (42.9% vs 67.8%).
- A small study published in 2020 (N=302) found that the addition of renal denervation to catheter ablation increased the success rate of catheter ablation at 12 months (72% with vs 56% without). [PMID 31961420]
- Efficacy (clinical outcomes)
- A large study (N=2204) detailed below compared ablation to antiarrhythmics for a number of clinical outcomes (death, disabling stroke, serious bleeding, cardiac arrest). The trial found no clear benefit of ablation over meds (see CABANA study)
- A small study (N=363) that enrolled patients with NYHA class II - IV heart failure found that ablation was superior to medical therapy for a composite outcome of death from any cause or hospitalization for worsening heart failure ( see CASTLE-AF study).
- Recommendations
- The AFFIRM study enrolled 4060 patients with atrial fibrillation
Main inclusion criteria
- Age ≥ 65 years
- A fib deemed to be recurrent and likely symptomatic
- Additional risk factors for stroke or death
Baseline characteristics
- Average age 70 years
- Hypertension - 51%
- CAD - 26%
- History of CHF - 23%
- Previously failed antiarrhythmic drug - 17.6%
Randomized treatment groups
- Group 1 (2027 patients) - Rate control only with beta blockers, calcium channel blockers, and/or digoxin. Target rate was ≤ 80 bpm resting and ≤ 110 bpm with six-minute walk test. Continuous anticoagulation with warfarin was mandated.
- Group 2 (2033 patients) - Rhythm control with common antiarrhythmic drugs. Cardioversion as needed. Anticoagulation with warfarin could be stopped if sinus rhythm was maintained for 4 - 12 weeks.
Primary outcome: Overall mortality
Results
Duration: Average of 3.5 years | |||
Outcome | Rate control | Rhythm control | Comparisons |
---|---|---|---|
Primary outcome | 25.9% | 26.7% | p=0.08 |
Stroke or brain bleed | 7.4% | 8.9% | p=0.93 |
Any hospitalization | 73% | 80% | p<0.001 |
|
Findings: Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy, and there are potential advantages,
such as a lower risk of adverse drug effects, with the rate-control strategy. Anticoagulation should be continued in this group of high-risk patients.
- The EAST-AFNET 4 trial enrolled 2789 patients with A fib diagnosed within the past 12 months
Main inclusion criteria
- Age ≥ 18 years
- A fib diagnosed within last 12 months
- Age > 75 years OR previous TIA/Stroke OR meet two of the following: age > 65 years, female sex, heart failure, hypertension, diabetes mellitus, severe CAD, chronic kidney disease (GFR 15 - 59 ml/min), LVH
Baseline characteristics
- Average age 70 years
- Previous stroke or TIA - 12%
- Average CHA2DS2-VASc score - 3.4
- Median days since A fib diagnosis - 36
- Absence of A fib symptoms - 30%
- A fib type: First episode - 38% | Paroxysmal - 36% | Persistent - 26%
Randomized treatment groups
- Group 1 (1395 patients): Early rhythm control which consisted of antiarrhythmic drugs or ablation, as well as cardioversion of persistent atrial fibrillation soon after randomization
- Group 2 (1394 patients): Rate control therapy without rhythm control therapy. Rhythm control therapy was used only to mitigate uncontrolled atrial fibrillation–related symptoms during adequate rate control therapy.
- Treatment of cardiovascular conditions, anticoagulation, and rate control were mandated in all patients in accordance with guideline recommendations
Primary outcomes
- First: Composite of death from cardiovascular causes, stroke (either ischemic and hemorrhagic), or hospitalization with worsening of heart failure or acute coronary syndrome, analyzed in a time-to-event analysis
- Second: Number of nights spent in the hospital per year
Results
Duration: Median of 5.1 years | |||
Outcome | Rhythm control | Rate control | Comparisons |
---|---|---|---|
First primary outcome (%/year) | 3.9% | 5% | HR 0.79 (0.66 - 0.94) |
Secondary primary outcome (nights) | 5.8 | 5.1 | p=0.23 |
Stroke (%/year) | 0.6% | 0.9% | HR 0.65 (0.44 - 0.97) |
Death from CV causes (%/year) | 1.0% | 1.3% | HR 0.72 (0.52 - 0.98) |
Hospitalization for heart failure (%/year) | 2.1% | 2.6% | HR 0.81 (0.65 - 1.02) |
Hospitalization for coronary syndrome (%/year) | 0.8% | 1.0% | HR 0.83 (0.58 - 1.19) |
Overall mortality | 9.9% | 11.8% | N/A |
|
Findings: Early rhythm control therapy was associated with a lower risk of cardiovascular
outcomes than usual care among patients with early atrial fibrillation and cardiovascular conditions
- The CABANA study enrolled 2204 patients with symptomatic A fib
Main inclusion criteria
- New onset or under-treated paroxysmal, persistent, or long-standing persistent A fib
- Age ≥ 65 years or < 65 years with ≥ 1 stroke risk factor
Main exclusion criteria
- Failed ≥ 2 antiarrhythmic drugs
- NYHA class IV heart failure
Baseline characteristics
- Median age 68 years
- Median CHA2DS2-VASc score - 3
- Median length of time since diagnosis - 1.1 years
- A fib type: persistent 47% | paroxysmal 43% | long-standing persistent 10%
- Past antiarrhythmic use: one drug 82% | ≥ 2 drugs 18%
Randomized treatment groups
- Group 1 (1108 patients): Catheter Ablation
- Group 2 (1096 patients): Drug therapy
- It was recommended that patients randomized to medical therapy receive rate control medications first. If the patient had previously failed rate control therapy, then rhythm control drug therapy could be initiated in an approach consistent with contemporaneous guidelines.
- All patients were to receive anticoagulation based on contemporaneous guidelines. Patients who received a catheter ablation were treated with anticoagulation for at least 3 months after the ablation, with a recommendation that this be continued throughout the trial in patients with CHA2DS2-VASc score ≥ 2
Primary outcome: Composite of death, disabling stroke, serious bleeding, or cardiac arrest
Results
Duration: Median of 48.5 months | |||
Outcome | Ablation | Drug therapy | Comparisons |
---|---|---|---|
Primary outcome | 8% | 9.2% | HR 0.86 (0.65 - 1.15), p=0.30 |
Death | 5.2% | 6.1% | HR 0.85 (0.60 - 1.21), p=0.38 |
Disabling stroke | 0.3% | 0.6% | HR 0.42 (0.11 - 1.62), p=0.19 |
Serious bleeding | 3.2% | 3.3% | HR 0.98 (0.62 - 1.56), p=0.93 |
Cardiac arrest | 0.6% | 1.0% | HR 0.62 (0.24 - 1.61), p=0.33 |
|
Findings: Among patients with A fib, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite endpoint of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated
treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial.
- The CASTLE-AF trial enrolled 363 patients with NYHA class II - IV heart failure and A fib
Main inclusion criteria
- Symptomatic paroxysmal or persistent A fib
- EF ≤ 35%
- NYHA class ≥ II
- Dual chamber ICD implanted
Main exclusion criteria
- Left atrial diameter > 6 cm
- Previous ablation
Baseline characteristics
- Median age - 64 years
- Median EF - 32%
- NYHA class: I - 11% | II - 59% | III - 28% | IV - 2%
- A fib type: Paroxysmal - 33% | Persistent - 67%
Randomized treatment groups
- Group 1 (179 patients): Ablation followed by warfarin for 6 months. After 6 months, treatment was at provider's discretion.
- Group 2 (184 patients): Medical therapy (rate or rhythm control) at provider's discretion. A rhythm control strategy was used in 30% of patients.
- All patients were required to have an implantable cardioverter–defibrillator (ICD) device or a cardiac resynchronization therapy defibrillator (CRT-D)
Primary outcome: Composite of death from any cause or hospitalization for worsening heart failure
Results
Duration: Median 37.8 months | |||
Outcome | Ablation | Medical therapy | 1 vs 2 |
---|---|---|---|
Primary outcome | 28.5% | 44.6% | HR 0.62, 95%CI [0.43 - 0.87], p=0.007 |
Overall mortality | 13.4% | 25% | HR 0.53, 95%CI [0.32 - 0.86], p=0.01 |
CHF hospitalization | 20.7% | 35.9% | HR 0.56, 95%CI [0.37 - 0.83], p=0.004 |
|
Findings: Catheter ablation for atrial fibrillation in patients with heart failure was associated with a significantly lower rate of a composite end point
of death from any cause or hospitalization for worsening heart failure than was medical therapy.
- The EARLY-AF trial enrolled 303 patients with symptomatic, paroxysmal, untreated atrial fibrillation
Main inclusion criteria
- Symptomatic A fib
- Persistent or paroxysmal A fib
- At least 1 episode on ECG within 24 months
Main exclusion criteria
- Permanent A fib
- Daily antiarrhythmic drug therapy
- NYHA class III - IV heart failure
- Hypertrophic cardiomyopathy
Baseline characteristics
- Average age 58 years
- Male sex - 70%
- Median years since diagnosis - 1
- Paroxysmal A fib - 95%
- Previous cardioversion - 39%
- Average CHA2DS2-VASc score - 1.9
- Anticoagulant: Warfarin - 4.5% | Other - 60%
Randomized treatment groups
- Group 1 (154 patients): Cryoablation. Median time to procedure after randomization was 50 days.
- Group 2 (149 patients): Antiarrhythmic drug therapy according to local practices
- After enrollment, all patients underwent insertion of an implantable cardiac monitor that continuously detected A fib
- Initial antiarrhythmic drugs used: Flecainide - 76.5% | Sotalol - 15.4% | Propafenone - 4.7% | Dronedarone - 3.4%
Primary outcome: First recurrence of any atrial tachyarrhythmia (atrial fibrillation, atrial flutter, or atrial tachycardia) lasting 30 seconds or longer between 91 and 365 days after the initiation of an antiarrhythmic drug or the catheter ablation procedure
Results
Duration: 1 year | |||
Outcome | Cryoablation | Antiarrhythmics | Comparisons |
---|---|---|---|
Primary outcome | 42.9% | 67.8% | p<0.001 |
Symptomatic A fib | 11% | 26.2% | HR 0.39 (0.22 – 0.68) |
Average % time in A fib | 0.6% | 3.9% | N/A |
|
Findings: Among patients receiving initial treatment for symptomatic, paroxysmal atrial fibrillation, there was a significantly lower rate of atrial fibrillation recurrence with catheter cryoballoon ablation than with antiarrhythmic drug therapy, as assessed by continuous cardiac rhythm monitoring.
- Patients from the EARLY-AF trial (N=303) were followed for an additional 2 years. Results from 3-years of follow-up are presented below. All patients had implantable loop recorders placed at the beginning of the trial.
Duration: 3 years | |||
Outcome | Cryoablation | Antiarrhythmics | Comparisons |
---|---|---|---|
Persistent A fib | 1.9% | 7.4% | HR 0.25, 95%CI (0.09 – 0.70) |
Any atrial tachyarrhythmia | 56.5% | 77.2% | HR 0.51, 95%CI (0.38–0.67) |
Median % time in A fib | 0% | 0.24% | N/A |
|
Findings: Initial treatment of paroxysmal atrial fibrillation with catheter cryoballoon ablation was associated with a lower incidence of persistent atrial fibrillation or recurrent atrial tachyarrhythmia over 3 years of follow-up than initial use of antiarrhythmic drugs.
- AHA recommendations for rhythm control
- Electrical cardioversion
- In pursuing a rhythm-control strategy, cardioversion is recommended for patients with A fib or atrial flutter as a method to restore sinus rhythm. If cardioversion is unsuccessful, repeated direct-current cardioversion attempts may be made after adjusting the location of the electrodes or applying pressure over the electrodes, or following administration of an antiarrhythmic medication.
- Electrical cardioversion is recommended when a rapid ventricular response to A fib or atrial flutter does not respond promptly to pharmacological therapies and contributes to ongoing myocardial ischemia, hypotension, or heart failure
- Electrical cardioversion is recommended for patients with A fib or atrial flutter and pre-excitation when tachycardia is associated with hemodynamic instability [12]
- Pharmacological cardioversion
- Flecainide, dofetilide, propafenone, and intravenous ibutilide are useful for pharmacological cardioversion of A fib or atrial flutter provided contraindications to the selected drug are absent
- Administration of oral amiodarone is a reasonable option for pharmacological cardioversion of A fib
- Propafenone or flecainide (“pill-in-the-pocket”) in addition to a beta blocker or nondihydropyridine calcium channel antagonist is reasonable to terminate A fib outside the hospital once this treatment has been observed to be safe in a monitored setting for selected patients
- Dofetilide therapy should not be initiated out of hospital owing to the risk of excessive QT prolongation that can cause torsades de pointes [12]
- Catheter ablation
- Catheter ablation is useful for symptomatic paroxysmal or persistent A fib refractory or intolerant to at least one class I or III antiarrhythmic medication when a rhythm control strategy is desired
- A fib catheter ablation may be reasonable in selected patients with symptomatic A fib and heart failure with reduced left ventricular EF to potentially lower mortality rate and reduce hospitalization for HF
- Catheter ablation may be a reasonable initial treatment strategy before medication in patients with symptomatic paroxysmal or persistent A fib
- A fib catheter ablation to restore sinus rhythm should not be performed with the sole intent of obviating the need for anticoagulation. See stopping anticoagulation post-ablation. [12,16]
- Summary
- Rate vs Rhythm control
- In the AFFIRM study, neither rhythm or rate control was shown to be superior to the other. The rhythm control group had significantly more hospitalizations and adverse events. The rhythm control group also had more than double the number of crossovers as the rate control group which speaks to the limited efficacy of antiarrhythmic medications. In the EAST-AFNET 4 trial, an early rhythm control strategy that mainly used antiarrhythmic medications (86.8%) was slightly superior to a rate control strategy for a composite of CVD outcomes (absolute risk difference of 1.1%). The number needed to treat for 1 person to benefit from a rhythm control strategy was 91.
- Ablation vs Meds
- In the CABANA study, catheter ablation was not significantly better than medical therapy for stroke or death in high-risk patients with A fib. The study had a high crossover rate with 28% of patients in the drug therapy group receiving ablation. In intention-to-treat analyses, high crossover rates can bias a study towards the null. The authors discuss the fact that their treatment-received analyses and per-protocol analyses showed ablation to be superior to drug therapy. Unfortunately, these types of analyses are also biased because it's likely that sicker patients did not ultimately receive ablation and healthier patients may have been drawn to it.
- In the CASTLE-AF study which only enrolled patients with NYHA class II - IV heart failure, ablation was superior to medical therapy for a composite outcome of death from any cause or hospitalization for worsening heart failure.
- The EARLY-AF trial found that ablation was superior to antiarrhythmics at preventing A fib recurrence over 3 years
- TREATMENT | Weight loss
- Overview
- A study published in 2013 found that significant weight loss lowered A fib symptom burden and occurrence. The study is summarized below.
- STUDY
- Design: Randomized, controlled trial (N=150 | length = 15 months) in overweight patients (average BMI 33) with symptomatic A fib
- Treatment: Weight loss intervention vs Control
- Primary outcome: Atrial Fibrillation Severity Scale scores: symptom burden and symptom severity (scale 3.25 [best] - 30 [worst])
- Results:
- Weight loss: Intervention - 31 lbs, Control - 8 lbs
- Primary outcome (point reduction): Intervention - 11.8, Control - 2.6 (p<0.001)
- Mean A fib episodes on 7-day Holter: Intervention - 0.62, Control - 2.0 (p<0.001)
- Mean duration of A fib on 7-day Holter (minutes): Intervention - 491, Control - 1546 (p<0.001)
- Findings: In this study, weight reduction with intensive risk factor management resulted in a reduction in atrial fibrillation symptom burden and severity and in beneficial cardiac remodeling. These findings support therapy directed at weight and risk factors in the management of atrial fibrillation.
- AHA recommendations
- For overweight and obese patients with AF, weight loss, combined with risk factor modification, is recommended [16]
- TREATMENT | Alcohol reduction
- Overview
- The study detailed below found that patients with A fib who reduced their alcohol intake had a lower burden of A fib
- Another study found that alcohol avoidance for a week lowered A fib incidence as detected by a smartphone. [PMID 34775507]
- STUDY
- Design: Randomized controlled trial (N=140 | length = 6 months) in patients with symptomatic paroxysmal or persistent A fib who consumed ≥ 10 alcoholic drinks per week
- Treatment: Abstain from alcohol vs Continue usual alcohol consumption
- Primary outcomes: Two primary endpoints were freedom from recurrence of atrial fibrillation (after a 2-week “blanking period”) and total atrial fibrillation burden (proportion of time in atrial fibrillation) during 6 months of follow-up
- Results:
- Primary outcome (freedom from recurrence): Abstinence - 47%, Continue - 27% (p=0.005)
- Primary outcome (median % time in A fib): Abstinence - 0.5%, Continue - 1.2% (p=0.01)
- Average alcohol intake during study: Abstinence - 2.1 drinks/week, Continue - 13.2 drinks/week
- Findings: Abstinence from alcohol reduced arrhythmia recurrences in regular drinkers with atrial fibrillation.
- STROKE PREVENTION
- Overview
- Two main risk assessment tools have been developed to help quantify the risk of stroke in patients with A fib
- The CHADS2 score which incorporates 5 patient variables was the first system used. It was later updated with the CHA2DS2-VASc score which incorporates 8 patient variables. The AHA guidelines from 2014 use the CHA2DS2-VASc system to make their recommendations.
- Both tools are outlined below along with the associated annual stroke risk for each score
- CHADS2 score
CHADS2 risk criteria | Score |
---|---|
Prior stroke, TIA, or thromboembolism | 2 |
Age ≥ 75 | 1 |
Hypertension | 1 |
Diabetes | 1 |
Heart Failure | 1 |
Annual risk of stroke based on CHADS2 score | |
---|---|
CHADS2 score | Annual Stroke Rate |
0 | 1.9% |
1 | 2.8% |
2 | 4% |
3 | 5.9% |
4 | 8.5% |
5 | 12.5% |
6 | 18.2% |
- CHA2DS2-VASc score
CHA2DS2-VASc risk criteria | Score |
---|---|
Prior stroke, TIA, or thromboembolism | 2 |
Age ≥ 75 | 2 |
Hypertension | 1 |
Diabetes | 1 |
Heart Failure | 1 |
Vascular disease (CAD or PVD) | 1 |
Age 65 - 74 | 1 |
Female sex | 1 |
Annual risk of stroke based on CHA2DS2-VASc score | |
---|---|
CHA2DS2-VASc SCORE | Annual Stroke Rate |
0 | 0% |
1 | 1.3% |
2 | 2.2% |
3 | 3.2% |
4 | 4.0% |
5 | 6.7% |
6 | 9.8% |
7 | 9.6% |
8 | 6.7% |
9 | 15.2% |
AHA stroke prevention recommendations in A fib | ||
---|---|---|
CHA2DS2-VASc score | ||
Men | Women | Treatment |
≥ 2 | ≥ 3 |
|
1 | 2 |
|
0 | 1 |
|
Patients with mechanical heart valves |
|
AHA recommendations for anticoagulation before and after cardioversion | ||
---|---|---|
Duration of A fib | CHA2DS2-VASc score | Recommendation |
≥ 48 hours or unknown | Any score |
|
< 48 hours | Men ≥ 2 Women ≥ 3 |
|
< 48 hours | Men - 0 Women - 1 |
|
≥ 48 hours or unknown and negative TEE | Any score |
|
|
- Anticoagulant + antiplatelet therapy
- Patients with atrial fibrillation who have coronary artery disease have indications for both anticoagulation and antiplatelet therapy
- Recommendations for treating these patients are covered at the links below
- STROKE PREVENTION | Atrial appendage closure
- Overview
- The left atrial appendage is an outpocketing in the left atrium (see atrial appendage). In patients with A fib, blood tends to pool in the appendage and form clots. The left atrial appendage is believed to be the source of > 90% of thromboses in A fib.
- The Watchman device, which is inserted during a procedure similar to a heart cath, closes off the appendage so that blood cannot pool. In 2019, a second generation of the Watchman device called Watchman FLX was released. Another device called the Amplatzer Amulet was approved in the U.S. in 2021 for the same purpose.
- The PROTECT AF study detailed below compared the Watchman device to warfarin, and the PRAGUE-17 trial compared Amulet and Watchman to Apixaban
- The PROTECT AF study enrolled 707 adults with nonvalvular A fib
Main inclusion criteria
- Paroxysmal, persistent, or permanent nonvalvular AF
- CHADS2 score ≥ 1
Main exclusion criteria
- Patent foramen ovale with atrial septal aneurysm and right-to-left shunt
Baseline characteristics
- Average age 72 years
- CHADS2 score: 1 ∼ 30% | 2 ∼ 35% | 3 ∼ 20% | 4 ∼ 9% | 5 ∼ 4%
- A fib category: paroxysmal - 41% | persistent - 21% | permanent - 36% | unknown - 1%
- A fib onset: < 1 year - 18% | ≥ 1 year - 76% | unknown - 5.5%
Randomized treatment groups
- Group 1 (463 patients) - Watchman® device insertion + warfarin for 45 days. If device was positioned correctly, then warfarin was stopped and clopidogrel + aspirin was taken up until 6 months post insertion, then aspirin alone indefinitely
- Group 2 (244 patients) - Warfarin with target INR of 2 - 3
Primary outcomes
- Efficacy: Composite of stroke, cardiovascular death, or systemic embolism
- Safety: Composite of major bleeding, pericardial effusion, or device embolization
Results
Duration: Average of 18 months | |||
Outcome | Watchman device | Warfarin | Comparisons |
---|---|---|---|
Primary efficacy outcome (%/year) | 3% | 4.9% | Rate ratio 0.62, 95%CI [0.35 - 1.25] |
Primary safety outcome (%/year) | 7.4% | 4.4% | Rate ratio 1.69, 95%CI [1.01 - 3.19] |
All-cause mortality (%/year) | 3% | 4.8% | Rate ratio 0.62, 95%CI [0.34 - 1.24] |
|
Findings: The efficacy of percutaneous closure of the LAA with this device was non-inferior to that of warfarin therapy. Although there was a higher rate of adverse safety
events in the intervention group than in the control group, events in the intervention group were mainly a result of periprocedural complications. Closure of the LAA might provide an alternative
strategy to chronic warfarin therapy for stroke prophylaxis in patients with non-valvular atrial fibrillation.
- All the participants in the PROTECT AF Study above were followed for an average of 3.8 years. Results from 3.8 years are presented in the table below.
Duration: Average 3.8 years | |||
Outcome | Watchman device | Warfarin | Comparisons |
---|---|---|---|
Primary efficacy outcome (%/year) | 2.3% | 3.8% | HR 0.61, 95%CI [0.38 - 0.97], p=0.04 |
Primary safety outcome (%/year) | 3.6% | 3.1% | HR 1.21, 95%CI [0.78 - 1.94], p=0.41 |
All-cause mortality | 14.5% | 21.5% | HR 0.66, 95%CI [0.45 - 0.98], p=0.04 |
Findings: After 3.8 years of follow-up among patients with nonvalvular AF at elevated risk for stroke, percutaneous LAA closure met criteria for both noninferiority and superiority, compared with warfarin,
for preventing the combined outcome of stroke, systemic embolism, and cardiovascular death, as well as superiority for cardiovascular and all-cause mortality.
- All the participants in the PROTECT AF Study above were followed for an average of 5 years. Results from 5 years are presented in the table below.
Duration: Average 5 years | |||
Outcome | Watchman device | Warfarin | Comparisons |
---|---|---|---|
Primary efficacy outcome (%/year) | 2.24% | 3.66% | p=0.04 |
Findings: These 5-year outcomes of the PREVAIL trial, combined with the 5-year outcomes of the PROTECT AF trial, demonstrate that LAAC with Watchman provides stroke
prevention in nonvalvular atrial fibrillation comparable to warfarin, with additional reductions in major bleeding, particularly hemorrhagic stroke, and mortality.
- STUDY
- Design: Randomized controlled trial (N=402 | length = median 19.9 months) in high-risk A fib patients with high-risk defined as history of bleeding requiring intervention or hospitalization, a history of a cardioembolic event while taking an anticoagulant, and/or a CHA2DS2-VASc of ≥ 3 and HAS-BLED of > 2
- Treatment: Atrial appendage closure (Amulet - 61% | Watchman - 36% | Watchman FLX - 2.8%) vs Direct oral anticoagulant (96% received apixaban)
- Primary outcome: Composite of stroke, TIA, systemic embolism, cardiovascular death, major or nonmajor clinically relevant bleeding, or procedure-/device-related complications
- Results:
- Primary outcome: Atrial appendage closure - 11%/year, Apixaban - 13.4%/year (p=0.44)
- There were no differences between groups for the components of the composite endpoint: all-stroke/TIA (HR: 1.00, 95%CI [0.40 to 2.51]), clinically significant bleeding (HR 0.81, 95%CI [0.44 to 1.52]) and cardiovascular death (HR 0.75, 95%CI [0.34 to 1.62])
- Findings: Among patients at high risk for stroke and increased risk of bleeding, left atrial appendage closure was noninferior to apixaban in preventing major atrial fib-related cardiovascular, neurological, and bleeding events
- AHA atrial appendage closure recommendations
- Percutaneous left atrial appendage occlusion may be considered in patients with A fib at increased risk of stroke who have contraindications to long-term anticoagulation
- Surgical occlusion of the left atrial appendage may be considered in patients with A fib undergoing cardiac surgery, as a component of an overall heart team approach to the management of A fib [16]
- Summary
- In the PROTECT AF study, the Watchman device was noninferior to warfarin, and in the PRAGUE-17 trial, Watchman and Amulet devices were noninferior to apixaban. A study that compared the first-generation Watchman to Amulet found that the devices were similar in terms of safety and efficacy. [PMID 34459659]
- A study published in 2021 randomized patients with A fib who were undergoing cardiac surgery to atrial appendage closure or none. The study found that closure lowered the risk of stroke and systemic embolism over an average of 3.8 years. [PMID 33999547]
- Atrial appendage closure appears to be a safe and effective form of stroke prevention for A fib patients. Patients who receive the devices must take aspirin indefinitely.
- STROKE PREVENTION | Antiplatelet therapy
- Overview
- The effect of antiplatelet therapy on outcomes in atrial fibrillation has been evaluated in a number of trials
- The first three studies detailed below compared antiplatelet therapy to anticoagulation. The fourth study compared dual antiplatelet therapy to aspirin alone.
- Anticoagulation has consistently been found to be superior to antiplatelet therapy for improving outcomes in A fib
- The BAFTA study enrolled 973 elderly patients with atrial fibrillation
Main inclusion criteria
- Age ≥ 75 years
- Atrial fibrillation or atrial flutter
Main exclusion criteria
- Rheumatic heart disease
- Major nontraumatic hemorrhage within 5 years
- History of intracranial hemorrhage
- Peptic ulcer disease
- BP > 180/110
Baseline characteristics
- Average age 81 years
- Taking warfarin - 40%
- Taking aspirin - 42%
- History of stroke or TIA - 13%
- CHADS2 score: 1 to 2 - 72% | 3 to 6 - 28%
Randomized treatment groups
- Group 1 (488 patients) - Warfarin (target INR 2-3)
- Group 2 (485 patients) - Aspirin 75 mg once daily
Primary outcome: Composite of any nonfatal disabling stroke (ischemic or hemorrhagic), intracranial hemorrhage, or clinically
significant arterial embolism
Results
Duration: Average 2.7 years | |||
Outcome | Warfarin | Aspirin | Comparisons |
---|---|---|---|
Primary outcome | 4.9% | 9.9% | HR 0.48, 95%CI [0.28 - 0.80], p=0.0027 |
Stroke (all) | 4.3% | 9.1% | HR 0.46, 95%CI [0.26 - 0.79], p=0.003 |
Hemorrhagic stroke | 0.5% | 0.4% | HR 1.15, 95%CI [0.29 - 4.77], p=0.83 |
Overall mortality | 22% | 22% | HR 0.95, 95%CI [0.72 - 1.26], p=0.73 |
Major hemorrhage | 5.1% | 5.2% | HR 0.96, 95%CI [0.53 - 1.75], p=0.90 |
Drug discontinuation | 33% | 24% | N/A |
|
Findings: These data support the use of anticoagulation therapy for people aged over 75 who have atrial fibrillation, unless there are contraindications or the patient
decides that the benefits are not worth the inconvenience.
- The AVERROES study enrolled 5599 patients with atrial fibrillation who were at increased risk of stroke
Main inclusion criteria
- Age ≥ 50 years
- Atrial fibrillation
- Deemed unsuitable for warfarin
- At least one of the following: prior stroke or TIA, age ≥ 75 years, hypertension, diabetes, NYHA class II - IV heart failure, EF ≤ 35%, or documented PAD
Main exclusion criteria
- Heart valve disease requiring surgery
- Recent major hemorrhage within 6 months or high risk of bleeding
- CrCl < 25 ml/min
Baseline characteristics
- Average age 70 years
- Average CHADS2 score - 2.0
- Prior stroke or TIA - 14%
- A fib class: paroxysmal - 27% | persistent - 21% | permanent - 52%
Randomized treatment groups
- Group 1 (2808 patients) - Apixaban 2.5 - 5 mg twice a day
- Group 2 (2791 patients) - Aspirin 81 - 324 mg once daily
Primary outcome: Occurrence of stroke (ischemic or hemorrhagic) or systemic embolism
Results
Duration: After an average follow-up of 1.1 years, the study was stopped early due to clear superiority of apixaban | |||
Outcome | Apixaban | Aspirin | Comparisons |
---|---|---|---|
Primary outcome | 1.8% | 4.0% | HR 0.45, 95%CI [0.32 - 0.62], p<0.001 |
Stroke | 1.0% | 3.8% | HR 0.46, 95%CI [0.33 - 0.65], p<0.001 |
Hemorrhagic stroke | 0.21% | 0.32% | HR 0.67, 95%CI [0.24 - 1.88], p=0.45 |
Overall mortality | 3.95% | 5.02% | HR 0.79, 95%CI [0.62 - 1.02], p=0.07 |
Major bleeding | 1.6% | 1.4% | HR 1.13, 95%CI [0.74 - 1.75], p=0.57 |
Findings: In patients with atrial fibrillation for whom vitamin K antagonist therapy was unsuitable, apixaban reduced the risk of stroke or systemic embolism without
significantly increasing the risk of major bleeding or intracranial hemorrhage.
- The ACTIVE W trial enrolled 6706 patients with A fib
Main inclusion criteria
- A fib + one of the following: age ≥ 75 years, treatment for hypertension, previous TIA/stroke, previous systemic embolism, EF < 45%, PAD, (patients 55 - 74 years with diabetes or CAD were also eligible)
Main exclusion criteria
- Peptic ulcer disease within previous 6 months
- Previous intracerebral hemorrhage
- Thrombocytopenia (< 50,000/mm³)
Baseline characteristics
- Average age 70 years
- Average CHA2DS2-VASc score - 2
- Duration of A fib > 2 years - 60%
- History of stroke/TIA - 15%
- A fib type: permanent - 69% | persistent - 13% | paroxysmal - 18%
Randomized treatment groups
- Group 1 (3335 patients) - Aspirin 75 - 100 mg once daily + Clopidogrel 75 mg once daily
- Group 2 (3371 patients) - Vitamin K antagonist (target INR of 2-3)
- Treatment was open-label
Primary outcome: Composite of stroke, non-CNS systemic embolism, myocardial infarction, or vascular death
Results
Duration: After a median follow-up of 1.28 years, the study was stopped early because of clear warfarin superiority | |||
Outcome (%/year) | ASA + Clopidogrel | Vitamin K antagonist | Comparisons |
---|---|---|---|
Primary outcome | 5.6% | 3.93% | HR 1.44, [1.18 - 1.76], p=0.0003 |
Stroke | 2.39% | 1.4% | HR 1.72, [1.24 - 2.37], p=0.001 |
Non-CNS systemic embolism | 0.43% | 0.10% | HR 4.66, [1.58 - 13.8], p=0.005 |
Myocardial infarction | 0.86% | 0.55% | HR 1.58, [0.94 - 2.67], p=0.09 |
Overall mortality | 3.8% | 3.76% | HR 1.01, [0.81 - 1.26], p=0.91 |
Severe and fatal hemorrhage | 2.42% | 2.21% | HR 1.10, [0.83 - 1.45], p=0.53 |
Primary outcome + major bleed | 7.56% | 5.45% | HR 1.41, [1.19 - 1.67], p<0.0001 |
Drug discontinuation | 13.8% | 7.8% | N/A |
|
Findings: Oral anticoagulation therapy is superior to clopidogrel plus aspirin for prevention of vascular events in patients with atrial fibrillation
at high risk of stroke, especially in those already taking oral anticoagulation therapy.
- The ACTIVE A trial enrolled 7554 patients with atrial fibrillation who were unsuited for vitamin K antagonists
Main inclusion criteria
- A fib + one of the following: age ≥ 75 years, hypertension, previous TIA/stroke, previous systemic embolism, EF < 45%, PAD, (patients 55 - 74 years with diabetes or CAD were also eligible)
Main exclusion criteria
- Peptic ulcer disease within previous 6 months
- Previous intracerebral hemorrhage
- Thrombocytopenia (< 50,000/mm³)
Baseline characteristics
- Average age 71 years
- Average CHADS2 score - 2
- Duration of A fib > 2 years - 53%
- History of stroke/TIA - 13%
- A fib type: permanent - 64% | persistent - 14% | paroxysmal - 22%
- Reason for not taking vitamin K antagonist: bleeding risk - 23% | doctor deemed inappropriate - 50% | patient declined - 26%
Randomized treatment groups
- Group 1 (3772 patients) - Clopidogrel 75 mg once daily + Aspirin 75 - 100 mg once daily
- Group 2 (3782 patients) - Placebo + Aspirin 75 - 100 mg once daily
Primary outcome: Composite of stroke, systemic embolism, myocardial infarction, or death from vascular causes
Results
Duration: Median of 3.6 years | |||
Outcome (%/year) | Clopidogrel | Placebo | Comparisons |
---|---|---|---|
Primary outcome | 6.8% | 7.6% | RR 0.89, 95%CI [0.81 - 0.98], p=0.01 |
Any stroke | 2.4% | 3.3% | RR 0.72, 95%CI [0.62 - 0.83], p<0.001 |
Myocardial infarction | 0.7% | 0.9% | RR 0.78, 95%CI [0.59 - 1.03], p=0.08 |
Overall mortality | 6.4% | 6.6% | RR 0.98, 95%CI [0.89 - 1.08], p=0.69 |
Major bleeding | 2.0% | 1.3% | RR 1.57, 95%CI [1.29 - 1.92], p<0.001 |
Any bleeding | 9.7% | 5.7% | RR 1.68, 95%CI [1.52 - 1.85], p<0.001 |
Findings: In patients with atrial fibrillation for whom vitamin K-antagonist therapy was unsuitable, the addition of clopidogrel to aspirin reduced the risk of
major vascular events, especially stroke, and increased the risk of major hemorrhage
- AHA recommendations
- The 2019 guidelines from the AHA do not mention aspirin as a therapy for stroke prevention in A fib
- Past AHA guidelines and the 2012 ACCP guidelines did include aspirin as a potential therapy in patients with a CHA2DS2-VASc score of 1 (AHA) or a CHADS2 score of 0 (ACCP)
- Summary
- Some patients with A fib refuse anticoagulant therapy because of the cost, blood testing, and other reasons. Although not ideal, aspirin and/or clopidogrel may be an option in these patients. The studies detailed above help to quantify the benefits and risks of antiplatelet therapy in A fib.
- STOPPING ANTICOAGULATION
- Stopping anticoagulation after cardioversion or ablation
- After A fib cardioversion or catheter ablation, the question arises as to whether a patient can stop their anticoagulation. Unfortunately, there are no good studies or guidelines to help make this decision. Further complicating the matter is the fact that A fib is often asymptomatic, so patients may be unaware that they are still having episodes. It is estimated that at least 50% of patients who undergo ablation will have a recurrence of A fib within 5 years.
- The decision to stop anticoagulation after successful cardioversion or catheter ablation is based on individual risk factors and the patient's willingness to accept unknown risks. The 2017 Heart Rhythm Society recommendations on anticoagulation after ablation are presented below. In cases where A fib is the result of a known correctable cause (ex. hyperthyroidism), anticoagulation may be stopped after the underlying disease has been corrected. [19]
- 2017 Heart Rhythm Society recommendations
- Systemic anticoagulation with warfarin or DOAC is recommended for at least 2 months post-ablation
- Adherence to A fib anticoagulation guidelines is recommended for patients who have undergone an A fib ablation procedure, regardless of the apparent success or failure of the procedure
- Decisions regarding continuation of systemic anticoagulation more than 2 months post-ablation should be based on the patient's stroke risk profile and not on the perceived success or failure of the ablation procedure
- Patients in whom discontinuation of anticoagulation is being considered based on patient values and preferences should consider undergoing continuous or frequent ECG monitoring to screen for A fib recurrence [19]
- Stopping anticoagulation before procedures
- Professional guidelines for stopping anticoagulants before procedures in patients with A fib are available at the link below
- POSTOPERATIVE ATRIAL FIBRILLATION
- Overview
- Atrial fibrillation is one of the most common complications after cardiac surgery, occurring in 20 - 50% of patients. Fortunately, 90% of patients return to sinus rhythm within days. The ideal treatment of postoperative A fib has not been defined. In 2016, a study was published that compared rate control to rhythm control in patients with postoperative A fib after CABG and/or heart valve surgery. The study is detailed below.
- The CTSN study randomized 523 patients with no prior history of A fib who experienced A fib after cardiac surgery
Main inclusion criteria
- Postoperative A fib that persisted for more than 60 minutes or recurrent episodes of A fib during the index hospitalization (≤ 7 days after surgery)
- Hemodynamically stable
- Underwent elective cardiac surgery to treat coronary artery disease or heart valve disease
Main exclusion criteria
- Prior history of A fib
Baseline characteristics
- Average age 69 years
- Heart valve disease - 55%
- Index procedure: CABG - 40%, valve repair - 16%, valve replacement - 24%, CABG + valve repair - 3.3% CABG + valve replacement - 16%
- Taking beta blocker - 59%
- Taking calcium channel blocker - 21%
Randomized treatment groups
- Group 1 (262 patients) - Rate control with a target resting heart rate < 100 bpm
- Group 2 (261 patients) - Rhythm control with amiodarone. If A fib persisted for 24 - 48 hours after randomization, direct current cardioversion was recommended.
- The average time to the onset of postoperative A fib was 2.4 days
- If patients remained in A fib or had recurrent A fib 48 hours after randomization, anticoagulation with warfarin (INR 2 - 3) was recommended, and bridging with LMWH was allowed. Anticoagulation was recommended to be continued for 60 days unless complications occurred.
Primary outcome: Total number of days in the hospital (including emergency department visits) within 60 days after randomization
Results
Duration: 60 days | |||
Outcome | Rate control | Rhythm control | Comparisons |
---|---|---|---|
Primary outcome (median # of days) | 5.1 days | 5.0 days | p=0.76 |
Hospital readmission (events/100 patient-months) | 18.5 | 18.5 | p=0.99 |
Stable heart rhythm (no A fib) at discharge | 89.9% | 93.5% | p=0.14 |
Stroke or TIA | 0.8% | 0.4% | p=0.40 |
Met criteria for anticoagulation | 46.2% | 31.8% | N/A |
Received direct-current cardioversion | 9.2% | 13.8% | N/A |
|
Findings: Strategies for rate control and rhythm control to treat postoperative atrial fibrillation were associated with equal numbers of days of hospitalization, similar
complication rates, and similarly low rates of persistent atrial fibrillation 60 days after onset. Neither treatment strategy showed a net clinical advantage over the other.
- AHA recommendations
- The AHA recommends rate control with a beta blocker as first-line treatment in patients who develop A fib after postoperative cardiac or thoracic surgery
- A nondihydropyridine calcium channel blocker is recommended as an alternative if a beta blocker is inadequate [14]
- Summary
- In the CTSN study, neither strategy (rate vs rhythm) was superior to the other for managing postoperative A fib. One takeaway from the study is that anticoagulation was started if A fib persisted for more than 48 hours, and it was continued for at least 60 days. This offers some guidance on when and how to anticoagulate these patients. Stroke and TIA events were low in both groups (<1%).
- A study published in 2021 found that posterior left pericardiotomy (to prevent pericardial effusion) after cardiac surgery significantly reduced the risk of postoperative A fib. [PMID 34788640]
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