CCS Atrial Fibrillation (AF) Guidelines (2010, 2012, 2014, 2016, and

The Canadian Cardiovascular Society’s

GUIDELINES

ATRIAL FIBRILLATION

UPDATE

About this Pocket Guide

This pocket guide is a quick-reference tool that features diagnostic and management recommendations based on the CCS

Atrial Fibrillation (AF) Guidelines (2010, 2012, 2014, 2016, and 2018).

These recommendations are intended to provide a reasonable and practical approach to the care for primary care physicians,

specialists, nurses and allied health professionals. Recommendations are subject to change as scientic knowledge and

technology advance and practice patterns evolve, and are not intended to be a substitute for clinical judgment. Adherence

to these recommendations will not necessarily produce successful outcomes in every case.

Recommendations were developed according to GRADE standards with the strength of recommendations now

classied as “Strong” or “Weak” (previously “Strong” or “Conditional”).

For the complete CCS Guidelines on AF, an updated summary of all standing CCS AF recommendations from 2010 to the

present 2018 Focused Update; or for additional resources, please visit www.ccs.ca.

Co-Chairs

Jason G. Andrade, Laurent Macle, and Atul Verma.

CCS Atrial Fibrillation Guideline Panel Members

Primary Panel: Clare Atzema, Alan Bell, John Cairns, Stuart Connolly, Jafna Cox, Paul Dorian, David Gladstone,

Jeff S. Healey, Kori Leblanc, M. Sean McMurtry, L. Brent Mitchell, Girish M. Nair, Stanley Nattel, Ratika Parkash,

Louise Pilote, Jean-Francois Sarrazin, Mike Sharma, Allan Skanes, Mario Talajic, Teresa Tsang, Subodh Verma,

D. George Wyse.

Secondary Panel: David Bewick, Vidal Essebag, Peter Guerra, Milan Gupta, Brett Heilbron, Paul Khairy, Bob Kiaii,

George Klein, Simon Kouz, Daniel Ngui, Pierre Page, Calum Redpath, Jan Surkes, and Richard Whitlock.

Table of Contents

Etiology and Clinical Investigation ...................................................................................................................................... 1

Integrated Approach to Risk Management ......................................................................................................................... 4

Rate and Rhythm Management .......................................................................................................................................... 6

Rate and Rhythm Management of AF in the Acute Care Setting ................................................................................ 12

“Pill-In-The-Pocket” Antiarrhythmic Drug Therapy ....................................................................................................... 13

Catheter Ablation of AF and Atrial Flutter ................................................................................................................... 14

Prevention of Stroke .......................................................................................................................................................... 15

“CCS Algorithm” (CHADS-65)...................................................................................................................................... 15

Dosage of OACs Based on Renal Function ................................................................................................................ 17

Reversal Agents for NOACs ....................................................................................................................................... 18

Special Considerations ....................................................................................................................................................... 19

Anticoagulation in the Context of AF and CAD ........................................................................................................... 19

Anticoagulation in the Context of Cardioversion ......................................................................................................... 25

Investigation and Management of Subclinical AF ....................................................................................................... 29

Etiology and Clinical Investigation

Baseline Evaluation for All Patients

HISTORY AND PHYSICAL EXAM

• Establish pattern (new onset, paroxysmal, persistent or permanent)

• Establish severity (including impact on quality of life)

• Identify etiology

• Identify reversible causes (hyperthyroidism, ventricular pacing,

supraventricular tachycardia, exercise, etc)

• Identify risk factors whose treatment could reduce recurrent AF

or improve overall prognosis (i.e. hypertension, sleep apnea, left

ventricular dysfunction, etc)

• Take social history to identify potential triggers (i.e. alcohol, intensive

aerobic training, etc)

• Elicit family history to identify potentially heritable causes of AF

(particularly lone AF)

• Determine thromboembolic risk

• Determine bleeding risk to guide appropriate antiplatelet or

antithrombotic therapy

• Review prior pharmacological therapy for AF, both for efcacy and

adverse effects

• Measure blood pressure and heart rate

• Determine patient height and weight

• Comprehensive precordial cardiac examination and assessment

of jugular venous pressure, carotid and peripheral pulses to detect

evidence of structural heart disease

12-LEAD ELECTROCARDIOGRAM

• Document presence of AF

• Assess for structural heart disease (myocardial infarction, ventricular

hypertrophy atrial enlargement, congenital heart disease) or electrical

heart disease (ventricular pre-excitation, Brugada syndrome)

• Identify risk factors for complications of therapy for AF (conduction

disturbance, sinus node dysfunction or abnormal repolarization)

• Document baseline PR, QT or QRS intervals

ECHOCARDIOGRAM

• Document ventricular size, wall thickness and function

• Evaluate left atrial size (if possible, left atrial volume)

• Exclude significant valvular or congenital heart disease (particularly

atrial septal defects)

• Estimate ventricular filling pressures and pulmonary arterial

pressure

LABORATORY INVESTIGATIONS

• Complete blood count

• Coagulation profile

• Renal function

• Thyroid and liver function

• Fasting lipid profile

• Fasting glucose

Additional Investigations for Selected Patients

Etiology and Clinical Investigation

Investigation Potential Role

Chest radiography

Exclude concomitant lung disease, heart failure

Baseline in patients receiving amiodarone

Ambulatory electrocardiography

(Holter, event, or loop monitor)

Document AF, exclude alternative diagnosis (atrial tachycardia, atrial utter, AVNRT/AVRT, venticular

tachycardia), establish symptom-rhythm correlation, assess venticular rate control

Treadmill exercise test

Investigation of patients with symptoms of coronary artery disease, assessment of ventricular rate

control

Transesophageal echocardiography

Rule out left atrial appendage thrombus, facilitate cardioversion in patients not receiving oral

anticoagulation, more precise characterization of structural heart disease (mitral valve disease, atrial

septal defect, cor triatriatum, etc.)

Electrophysiology study

Patients with documented regular supraventricular tachycardia (i.e. atrial tachycardia, AVNRT/AVRT,

atrial utter) that is amenable to catheter ablation

Serum calcium and magnesium

In cases of suspected deciency (i.e. diuretic use, gastrointestinal losses) which could inuence therapy

(i.e. sotalol)

Sleep study (overnight oximetry

or polysomnography)

In patients with symptoms of obstructive sleep apnea or in select patients with advanced symptomatic

heart failure

Ambulatory blood pressure monitoring In cases of borderline hypertension

Genetic testing

In rare cases of apparent familial AF (particularly with onset at a young age) with additionnal features of

conduction disease, Brugada syndrome or cardiomyopathy

Etiology and Clinical Investigation

Established Patterns and Severity of Atrial Fibrillation

Patterns of Atrial Fibrillation SAF Score*

SAF Score Impact on QOL**

Class 0 Asymptomatic

1 Minimal effect on QOL

2 Minor effect on QOL

3 Moderate effect on QOL

4 Severe effect on QOL

* Dorian P, Cvitkovic SS, Kerr CR; et al. Can J Cardiol. 2006; 22(5):383-386 ** QOL = Quality of life

Newly

Diagnosed

Persistent

episode

duration

≥

7 days

Permanent

Decision to forego

attempts at sinus

rhythm restoration

Paroxysmal

AF episode

duration < 7 days

Risk Markers and Co-morbid Conditions Associated with AF

Conventional Risk Factors Emerging Risk Factors Potential Risk Factors

• Advancing age

• Male Sex

• Hypertension

• HF with reduced ejection fraction

• Valvular heart disease

• Thyroid disease

• Obstructive sleep apnea

• Chronic obstructive pulmonary disease

• Excessive alcohol intake

• Pre-hypertension

• Increased pulse pressure

• HF with preserved ejection fraction

• Congenital heart disease

• Subclinical hyperthyroidism

• Obesity

• Coronary artery disease

• Morphometric (increased height,

increased birth weight)

• Excessive endurance exercise

• Familial / Genetic factors

• Tobacco Use

• Echocardiographic

(left atrial dilation, LV hypertrophy)

• Inammation

• Diabetes

• Pericardial fat

• Subclinical atherosclerosis

• Electrocardiographic (atrial conduction

delay, PR interval prolongation)

• Chronic kidney disease

Approach to Risk Management

• We suggest that, in addition to implementing appropriate rate or rhythm control measures, an approach targeting modiable risk markers

and conditions associated with AF should be applied to prevent recurrence of the arrhythmia and/or decrease its symptom burden (Weak

Recommendation, Low-Quality Evidence).

Values and preferences: The aggressive treatment of obesity and cardiometabolic risk markers/conditions (including hypertension, heart

failure, diabetes, sleep apnea) has been shown to reduce AF burden and improve quality of life. This recommendation places a high value on the

recognized association between these potential risk markers and conditions that are known to aggravate AF, and the possibility that treatment

of these conditions might result in improvement of patient symptoms through reduction of AF burden and/or regression of the substrate that

causes AF.

• We recommend systematic and strict guideline-adherent management of traditional modiable cardiovascular risk factors and/or conditions

associated with AF, to reduce cardiovascular events (e.g. stroke, MI, etc.) (Strong Recommendation, High-Quality Evidence).

Approach to Risk Management

Modiable Cardiovascular Risk Factors

Management of modiable risk factors to reduce cardiovascular events

Management of modiable risk factors to reduce AF burden

Values and preferences: This recommendation places a high value on a systematic approach to providing guideline-directed therapy for any

cardiovascular risk factors and/or conditions associated with AF.

Practical tip: The detection and optimal management of risk factors and concomitant disorders together with appropriate rate/rhythm control

and stroke prevention may contribute to a reduction in cardiovascular-related emergency department visits and hospitalizations. Addressing

such risk factors might be most comprehensively and efciently accomplished through a specialized clinic or other multidisciplinary management

approach, and through a standardized, systematic protocol-based approach.

Overview of AF Management

Assessment of

Thromboembolic Risk

(CHADS-65)

AF Detected

Appropriate

Antithrombotic

Therapy

Management of

Arrhythmia

Detection and

Treatment of

Precipitating Causes

Rhythm

Control

Rate

Control

Major Goals of AF/AFL Arrhythmia Management

• Identify and treat underlying structural heart disease and other predisposing conditions

• Relieve symptoms

• Improve functional capacity/quality of life

• Reduce morbidity/mortality associated with AF/AFL

P Prevent tachycardia-induced cardiomyopathy

P Reduce/prevent emergency room visits or hospitalizations secondary to AF/AFL

• Prevent stroke or systemic thromboembolism

Rate and Rhythm Management

Algorithm for Rate vs Rhythm Control for Patients with Symptomatic AF

CONTINUE

RATE CONTROL

Persistent

Paroxysmal AF

ATTEMPT RATE CONTROL

Beta-blocker

Calcium channel blocker

SYMPTOMS RESOLVE

Low AF burden

Pill in pocket

anti-arrhythmic

therapy

High AF burden

Catheter ablation

Observe. If AF recurs, determine if symptomatic

Consider cardioversion

Symptoms

improve but

AF recurs

Symptoms

improve, and patient

maintains sinus

rhythm

Symptoms

don’t change in

sinus rhythm and

AF recurs

Maintenance

anti-arrhythmic

therapy

MODIFY RATE CONTROL -

CONSIDER RHYTHM CONTROL

Special circumstances to consider

early rhythm control:

• Highly symptomatic

• Multiple recurrences

• Extreme QOL impairment

• Arrhythmia induced cardiomyopathy

SYMPTOMATIC AF

Rate and Rhythm Management

Overview of Rate Management

Rate and Rhythm Management

Beta-Blockers

± Digoxin

Beta-Blockers*

CCB

∆

Combination Rx

Beta-Blockers*

CCB

∆

Digoxin

≠

Combination Rx

Heart Failure

CAD

No Heart Failure

or CAD

Drugs are listed in alphabetical order

* Beta-Blockers preferred in CAD

∆ Non-dihydropyridine calcium channel blockers (diltiazem, verapamil)

≠ Digoxin can be considered for rate control in patients who are sedentary

Rate Control Drug Choices

• We suggest that digoxin can be considered as a therapeutic option to achieve rate-control in patients with AF and symptoms caused

by rapid ventricular rates whose response to beta-blockers and/or calcium channel blockers is inadequate, or in whom such rate-

controlling drugs are contraindicated or not tolerated (Conditional Recommendation, Moderate-Quality Evidence).

Managing Rate Control – Recommended Drugs

ß-Blockers

Drug Dose Potential side-effects

Atenolol 50 – 150 mg p.o. daily Bradycardia, hypotension, fatigue, depression, bronchospasm

Bisoprolol 2.5 – 10 mg p.o. daily As per atenolol

Metoprolol 25 – 200 mg p.o. bid As per atenolol

Nadolol 20 – 160 mg p.o. daily - bid As per atenolol

Propranolol 80 – 240 mg p.o. bid - tid As per atenolol

Calcium Channel Blockers

Drug Dose Potential side-effects

Verapamil

240 – 480 mg/day p.o. divided tid - qid (short acting)

120 – 320 mg p.o. daily (long acting)

Bradycardia, hypotension, constipation

Diltiazem

180 – 360 mg/day p.o. divided tid - qid (short acting)

120 – 320 mg p.o. daily (long acting)

Bradycardia, hypotension, ankle swelling

Digoxin

Drug Dose Potential side-effects

Digoxin 0.0625 mg – 0.25 mg p.o. daily Bradycardia, nausea, vomiting, visual disturbance

Rate and Rhythm Management

Overview of Rhythm Management

Dronedarone

Flecainide

‡

Propafenone

‡

Sotalol

Catheter

ablation

Catheter ablation

Amiodarone

Sotalol*

Amiodarone

Drugs are listed in alphabetical order

+ Dronedarone should be used with caution in combination with digoxin

‡ Class I agents should be AVOIDED in CAD and should be COMBINED with

AV-nodal blocking agents

# Sotalol should be used with caution in those at risk for torsades de pointes VT

(e.g. female sex, age < 65 yr, taking diuretics)

* Sotalol should be used with caution with EF 35-40% and those at risk for

torsades de pointes VT (e.g. female sex, age < 65 yr, taking diuretics)

Rhythm Control Choices

No History of CHF

Normal Systolic Function

Rhythm Control Choices

History of CHF or

Left Ventricular Systolic Dysfunction

EF > 35% EF < 35%

Rate and Rhythm Management

Managing Rhythm Control – Recommended Drugs

Drug/Dose Efcacy Toxicity Comments

Flecainide

50 – 150 mg

BID

30 – 50%

Ventricular tachycardia

Bradycardia

Rapid ventricular response to AF or

atrial utter (1:1 conduction)

Contraindicated in patients with CAD or LV dysfunction

Should be combined with an AV nodal blocking agent

Propafenone

150 – 300 mg

TID

30 – 50%

Ventricular tachycardia

Bradycardia

Rapid ventricular response to AF

or atrial utter (1:1 conduction)

Abnormal taste

Contraindicated in patients with CAD or LV dysfunction

Should be combined with an AV nodal blocking agent

Amiodarone

100 – 200 mg

OD (after 10g

loading)

60 – 70%

Photosensitivity, Bradycardia,

GI upset, Thyroid dysfunction,

Hepatic toxicity, Neuropathy,

Tremor, Pulmonary toxicity,

Torsades de pointes (rare)

Low risk of proarrhythmia

Limited by systemic side effets

Most side effects are dose & duration related

Dronedarone

400 mg BID

40%

GI upset

Bradycardia,

Hepatic toxicity

Should not be used for rate control or for rhythm control in patients with a

history of CHF or LVEF < 40%

Should be used with caution when added to digoxin

Liver enzyme monitoring required

Limited experience outside clinical trials

Sotalol

80 – 160 mg BID

30 – 50%

Torsades de pointes

Bradycardia

Beta-Blocker side effects

Should be avoided in patients at high risk of torsades de pointes VT –

especially women > 65 years taking diuretics or those with renal insufciency

QT interval should be monitored 1 week after starting

Use cautionly when LVEF < 40%

Rate and Rhythm Management

Rate and Rhythm Management of AF in the Acute Care Setting

Recommended IV Drugs for Rate Control

Drug Dose Risks

Metoprolol 2.5-5 mg IV bolus over 2 min; up to 3 doses Hypotension, bradycardia

Diltiazem* 0.25 mg/kg IV over 2 min; repeat at 0.35 mg/kg IV after 15 min. Hypotension, bradycardia

Verapamil* 0.075-0.15 mg/kg over 2 min. Hypotension, bradycardia, bronchospasm

Digoxin 0.25 mg IV each 2 h; up to 1.5 mg Bradycardia, Digitalis toxicity

Recommended Drugs for Cardioversion

Medication Dose Time to Conversion Risks

Class Ia

Procainamide

15-18 mg/kg IV over

30-60 minutes

~60 minutes

Hypotension, Bradycardia

Ventricular proarrhythmia

Class Ic

Flecainide

Propafenone

300 mg po (> 70 kg)

200 mg po (≤ 70 kg)

600 mg po (> 70 kg)

450 mg po (≤ 70 kg)

2-6 hours

Hypotension

Bradycardia and conversion pauses

1:1 conduction of atrial utter*

Class III

Ibutilide

1 mg IV over 10 min

May repeat x 1

30-60 minutes

QT prolongation, Torsades de pointes**

Hypotension

Amiodarone

150 mg IV bolus then

60 mg/h x 6 hours then

30 mg/h x 18 hours

8-12 hours

Hypotension

Bradycardia, Atrioventricular block

Torsades de pointes

Phlebitis

Vernakalant

3 mg/kg IV over 10 minutes, followed by

2 mg/kg IV if no conversion

12-30 minutes

Hypotension, Bradycardia

Non-sustained ventricular tachycardia***

*Class Ic drugs (ecainide and propafenone) should be used in combination with AV nodal blocking agents (beta-blockers or calcium channel inhibitors). Class IC agents should be avoided in patients with ischemic heart

disease or signicant structural heart disease

**Consider pre-treating with 1-4 g of IV MgSO4. Ibutilide should be avoided in patients with hypokalemia, baseline QT prolongation, or signicant structural heart disease

***Vernakalant should be avoided in patients with hypotension, recent ACS, or signicant structural heart disease

* Calcium-channel blockers should not be used in patients with heart failure or left ventricular dysfunction

Rate and Rhythm Management

“Pill-In-The-Pocket” Antiarrhythmic Drug Therapy

AAD, antiarrhythmic drug; AF, atrial brillation; AV, atrioventricular; BP, blood pressure; ECG, electrocardiogram; ED, emergency department; PIP, “pill-in-the-pocket”.

Rate and Rhythm Management

Appropriate candidates for PIP

1) patients with symptomatic AF

2) sustained AF episodes (e.g. ≥ 2 hours)

3) AF episodes that occur less frequently than monthly

4) absence of severe or disabling symptoms during an AF episode

(e.g. fainting, severe chest pain, or breathlessness)

ability to comply with instructions, and proper medication use

Determinants of initial treatment failure

1) AF persistence > 6 hours after PIP-AAD administration or electrical

cardioversion required for termination

2) Adverse events including symptomatic hypotension (systolic BP ≤ 90

mmHg), symptomatic conversion pauses (> 5 seconds), symptomatic

bradycardia after sinus rhythm restoration, pro-arrhythmia (conversion to

atrial utter/tachycardia, or episodes of ventricular tachycardia), severe

symptoms (dyspnea, presyncope, syncope), or a > 50% increase in QRS

interval duration from baseline.

Instructions for subsequent out-of-hospital use

1) Patients should take the AV nodal agent 30 minutes after the perceived arrhythmia

onset, followed by the Class Ic AAD 30 minutes following the AV nodal agent.

2) Following AAD administration patients should rest in a supine or seated

position for the next 4 hours, or until the episode resolves.

Patients should present to the emergency department in the event that:

a) the AF episode did not terminate within 6-8 hours

b) they felt unwell after taking the medication at home (e.g. a subjective worsening

of the arrhythmia following AAD ingestion, or if they developed new or severe

symptoms such as dyspnea, presyncope, or syncope)

c) more than one episode occurred in a 24-hour period (patients should not take a

second PIP-AAD dose within 24 hours)

d) if the AF episode was associated with severe symptoms at baseline (e.g.

signicant dyspnea, chest pain, pre-syncope, or symptoms of stroke), even in

the absence of PIP-AAD use.

PIP administration

Immediate release oral AV nodal blocker (one of diltiazem 60 mg, verapamil

80 mg, or metoprolol tartrate 25 mg) 30 minutes prior to the administration of

a class Ic AAD (300 mg of ecainide or 600 mg of propafenone if ≥ 70 kg; 200

mg of ecainide or 450 mg of propafenone if < 70 kg)

Initial ED monitoring

Telemetry for at least 6 hours

Blood pressure monitoring every 30 minutes

12-lead ECG monitoring every 2 hours

Contraindication to PIP

1) signicant structural heart disease (e.g. left ventricular systolic dysfunction

[LVEF < 50%], active ischemic heart disease, severe left ventricular hypertrophy)

abnormal conduction parameters at baseline (e.g. QRS duration > 120 msec, PR

interval > 200 msec; or evidence of pre-excitation)

3) clinical or electrocardiographic evidence of sinus node dysfunction/bradycardia or

advanced AV block

4) hypotension (systolic BP < 100mmHg)

5) prior intolerance to any of the PIP-AAD medications

Catheter Ablation

Risk/Benet Ratio* for Ablation in Patients with Symptomatic AF

Longstanding

Persistent Paroxysmal

1st line -- -- +

Failed 1st drug -- + + +

Failed 2nd drug + + + + + +

Failed multiple drugs + + + + + + + +

• We recommend catheter ablation of AF in patients who remain symptomatic following an adequate trial of antiarrhythmic drug therapy and in

whom a rhythm control strategy remains desired (Strong Recommendation, Moderate-Quality Evidence).

• We recommend curative catheter ablation for symptomatic patients with typical atrial utter as rst line therapy or as a reasonable alternative

to pharmacologic rhythm or rate control therapy (Strong Recommendation, Moderate-Quality Evidence).

• We suggest catheter ablation to maintain sinus rhythm as rst-line therapy for relief of symptoms in highly selected patients with symptomatic,

paroxysmal atrial brillation (Conditional Recommendation, Moderate-Quality Evidence).

• We suggest that catheter ablation may be performed using uninterrupted therapeutic oral anticoagulation with either a NOAC or adjusted-dose

warfarin (Weak Recommendation, Moderate-Quality Evidence).

* irrespective of the presence or absence of HF or ventricular dysfunction

+ indicates balance of benet to risk in favour of catheter ablation

¶ ongoing symptomatic AF ≥ 1 year

Prevention of Stroke in AF and Atrial Flutter

Prevention of Stroke

OAC

Antiplatelet

therapy

Yes

No Antithrombotic

A NOAC is preferred over warfarin for non-valvular AF

Therapeutic options include single antiplatelet therapy

(ASA 81-100 mg daily) alone; or in combination with

either a second antiplatelet agent (e.g. clopidogrel 75

mg daily or ticagrelor 60 mg bid), or an antithrombotic

agent (rivaroxaban 2.5 mg bid).

The “CCS Algorithm” (CHADS-65)

for OAC Therapy in AF

Age > 65 years

Coronary artery disease or

Peripheral arterial disease

Prior Stroke or

TIA or

Hypertension or

Heart failure or

Diabetes Mellitus

(CHADS

risk factors)

• We recommend that when OAC-therapy is indicated for patients with non-valvular AF, most patients should receive dabigatran, rivaroxaban,

apixaban or edoxaban in preference to warfarin (Strong Recommendation, High-Quality Evidence).

Values and preferences: This recommendation places a relatively high value on the greater ease of use of the NOACs in comparison to

warfarin, and the results of large RCTs showing that the NOACs are either non-inferior or superior to warfarin in stroke prevention; the drugs

have no more major bleeding or less bleeding vs warfarin and especially less intracranial hemorrhage. The recommendation places less value

on the shorter clinical experience, lack of a specic antidote, and lack of a simple test for intensity of anticoagulant effect with the NOACs.

The preference for one of the NOACs over warfarin is less marked among patients already receiving warfarin with stable therapeutic INRs, no

bleeding complications, and who are not requesting a change in OAC therapy.

• For patients with non-valvular AF/AFL aged < 65 years with no CHADS

risk factors, we suggest no antithrombotic therapy for stroke

prevention (Weak Recommendation, Moderate-Quality Evidence), with management of their coronary or arterial vascular disease as directed

by the 2018 CCS/CAIC Focused Update of the Guidelines for the Use of Antiplatelet Therapy.

Practical tip: For patients with non-valvular AF/AFL aged < 65 years with no CHADS

risk factors, the risk of stroke associated with AF is

not sufciently elevated to justify OAC therapy. For this group treatment should be directed at the underlying coronary/peripheral arterial

disease as outlined in the 2018 CCS/CAIC Focused Update of the Guidelines for the Use of Antiplatelet Therapy. Therapeutic options include

ASA 81-100 mg daily alone; or ASA in combination with either clopidogrel 75 mg daily, ticagrelor 60 mg BID, or rivaroxaban 2.5 mg BID.

Prevention of Stroke in AF and Atrial Flutter

No OAC therapy for patients < 65 years with no CHADS

risk factors and antiplatelet therapy for those patients with coronary or

arterial vascular disease

Most patients should receive NOAC

Prevention of Stroke

Dosage of Oral Anticoagulants Based on Renal Function

CrCl Warfarin Dabigatran Rivaroxaban Apixaban Edoxaban

CrCl >50 mL/min

Dose adjusted for

INR 2.0-3.0

150 mg bid* 20 mg daily 5 mg bid 60 mg daily∞

CrCl 30-49 mL/min

Dose adjusted for

INR 2.0-3.0

Consider 110 mg bid in

preference to 150 bid

15 mg daily

5 mg bid

(Consider 2.5 mg bid)

†

30 mg daily

CrCl 15-29 mL/min No RCT Data ** No RCT Data

No RCT Data

Very limited

RCT Data

No RCT Data

CrCl < 15 mL/min

(or on dialysis)

No RCT Data

‡

No RCT Data

bid, twice daily; INR, international normalized ratio; RCT, randomized clinical trial.

* Consider Dabigatran 110 mg po bid if age >75 years

† Consider Apixaban 2.5 mg po bid if 2 of the 3 following criteria are present: 1) age >80 years, 2) body weight <60 kg, or 3) serum creatinine >133 цmol/L

∞ Consider Edoxaban 30mg daily if weight ≤60 kg or concomitant potent P-Gp inhibitor therapy

** Dose adjusted warfarin has been used, but data regarding safety and efcacy is conicting

‡ Dose adjusted warfarin has been used, but data regarding safety and efcacy is conicting and may lean towards causing harm.

§ The ARISTOTLE trial did include patients with a CrCl as low as 25 mL/min, but this was a very small number of patients (1.5% of patients in the trial).

¶ No published randomised studies support a dose for this level of renal function; product monographs suggest the drug is contraindicated for this level of renal function.

Prevention of Stroke

• We recommend administering idarucizumab for emergency reversal of dabigatran’s anticoagulant effect in patients with uncontrollable

or potentially life-threatening bleeding and/or in patients who require urgent surgery for which normal hemostasis is necessary (Strong

Recommendation, Moderate-Quality Evidence).

Values and preferences:

This recommendation places relatively greater value on the ability of idarucizimab to reverse coagulation parameters

indicative of dabigatran’s effect, its potential to decrease bleeding-related outcomes and risks of urgent surgery, and its safety and tolerability

prole, and less value on the absence of a control group in the REVERSE-AD trial and on the cost of the drug.

Reversal Agents for NOACs - Recommendation

Idarucizimab for emergency reversal of dabigatran’s anticoagulant effect

Practical tips:

•

In acute, life-threatening bleeding situations in which standard resuscitation (such as local measures, transfusion, etc) is anticipated to be

insufcient (eg, intracranial hemorrhage), or in situations in which standard resuscitation has not stabilized the patient, idarucizumab 5g IV should

be administered as soon as possible. Activated partial thromboplastin time (aPTT) and thrombin time (TT) may be used to qualitatively identify

the presence of active dabigatran at baseline in a patient, although they are less sensitive than dilute thrombin time (DTT) and ecarin clotting time

(ECT; 92% of patients in the REVERSE-AD trial had an elevated DTT or ECT,whereas only 74% had an elevated aPTT). However, obtaining these

measures should not delay the administration of idarucizumab. In many instances of life-threatening bleeding, clinicians have to make a treatment

decision on the basis of a history of dabigatran use rather than laboratory evidence. Renal function and timing of the last dose of dabigatran

provide key information regarding the likely extent of remaining dabigatran effect.

• “Urgent” surgery as dened in the REVERSE-AD trial is surgery that cannot be delayed beyond 8 hours (amended from 4 hours in the initial

version of the protocol). The timing of surgery should be based on the clinical indication and stability of the patient. In instances where delayed

surgery is appropriate, clinicians may obtain coagulation parameters (e.g.TT or aPTT) to identify patients who would be unlikely to benet

from idarucizumab.

• Reversing dabigatran therapy exposes patients to the thrombotic risk of their underlying disease. Oral anticoagulation should be reintroduced

as soon as medically appropriate.

Prevention of Stroke

Antithrombotic Therapy in Patients with AF and CAD or Vascular Disease

Anticoagulation in the Context

of AF and CAD

AF Patients with Coronary or Peripheral Arterial Disease and an

Indication for OAC (Age ≥ 65 or CHADS

≥ 1)

1. A PCI is considered high-risk based on clinical and angiographic features such as: diabetes mellitus, current smoker, chronic renal dysfunction (eGFR < 60 mL/min), prior ACS, prior stent thrombosis, multi-vessel disease, multiple

stents implanted, complex bifurcation lesion, total stent length > 60 mm, chronic total occlusion intervention, or bioabsorbable vascular scaffold (BVS) implantation.

2. Regimens evaluated in this context include: warfarin daily, rivaroxaban 15 mg PO daily (10 mg in patients with CrCl 30-50 mL/min), dabigatran 110 mg or 150 mg PO BID. A NOAC is preferred over warfarin, however if warfarin

is to be used the lower end of the recommended INR target range is preferred. All patients should receive a loading dose of ASA 160 mg at the time of PCI (if previously ASA naïve).

3. Regimens evaluated in this context include: warfarin daily, or rivaroxaban 2.5 mg PO BID. A NOAC is preferred over warfarin, however if warfarin is to be used the recommended INR target is 2.0-2.5. All patients should receive

a loading dose of ASA 160 mg at the time of PCI (if previously ASA naïve). Thereafter, ASA may be discontinued as early as the day following PCI or it can be continued longer term (e.g. 1 to 6 months after PCI). The timing of

when to discontinue ASA will depend on the individual patient’s ischemic and bleeding risk.

4. The dose of OAC beyond year after PCI should be the standard stroke prevention dose. Single antiplatelet therapy with ASA or clopidogrel may be added to OAC if high-risk clinical or angiographic features of ischemic events

and low risk of bleeding.

Elective PCI without

High Risk features

for thrombotic CV events

Dual Therapy

(OAC

+ Clopidogrel)

Duration:

1 to 12 months post BMS

3 to 12 months post DES

Stable CAD/PAD OAC

OAC

Dual Therapy

(OAC + Clopidogrel)

Duration:

up to 12 months post ACS

Triple Therapy

(OAC

+ ASA + Clopidogrel)

Duration: 1 day to 6 months

Dual Therapy

(OAC

+ Clopidogrel)

Duration:

up to 12 months post stent

ACS with PCI or Elective PCI

with High Risk Features for

thrombotic CV events

ACS without PCI

• When OAC is indicated in the presence of coronary or arterial vascular disease, we suggest a NOAC in preference to warfarin (Weak

Recommendation, Moderate-Quality Evidence).

Values and preferences:

The suggestion for use of a NOAC rather than warfarin places relatively greater weight on the ease of use of NOACs

versus warfarin, as well as the data from RCTs of NOACs versus warfarin for NVAF (e.g. equal or greater reduction of stroke, equal or greater

reduction in all-cause mortality, equal or less major bleeding, less intracranial bleeding and no net increase in CAD outcomes).

• We recommend that patients who have concomitant AF and coronary/arterial vascular disease (peripheral vascular disease or aortic plaque),

receive an antithrombotic therapy regimen that is based on a balanced assessment of their risk of AF-related stroke, ischemic coronary event,

and clinically relevant bleeding associated with the use of antithrombotic agents (Strong Recommendation, High-Quality Evidence).

Practical tip: For patients requiring combinations of antiplatelet and OAC agents for concomitant AF and coronary/arterial vascular disease, we

suggest that measures be employed to reduce the risk of bleeding, including: careful consideration of modiable bleeding risk factors with vigorous

efforts to mitigate them; consideration of proton pump inhibitor use; avoidance of prasugrel and ticagrelor in conjunction with OACs; the use of warfarin

in the lower target INR (e.g. 2.0-2.5); consideration of the lower effective doses of NOACs in selected patients (See Figure on page 19); specic

measures during coronary invasive procedures (radial access, small-diameter sheaths, early sheath removal from femoral site, and minimized use of

acute procedural anti-thrombotic therapies); delaying non-urgent procedures until dual pathway therapy is no longer required; use of walking aids for

those with gait or balance disorders; avoidance of NSAIDs or other drugs that may increase bleeding risk; and, strict blood pressure control.

Anticoagulation in the Context of AF and CAD

Antithrombotic therapy based on a balanced assessment of a patient’s risk of stroke

Most patients with an indication for OAC in the presence of CAD should receive a NOAC

Anticoagulation in the Context

of AF and CAD

Risk Factors Associated with an Increased Risk of Bleeding and Ischemic Coronary Outcomes

• Patient Factors

• Age (> 65 years)

• Low body weight (< 60 kg)

• Hypertension

• History of bleeding (esp. within 1y)

• Prior stroke or intracranial bleed

• Combined OAC and antiplatelet use

• Concomitant NSAID or prednisone use

• Excess alcohol consumption

• Abnormal liver function

• CKD (eGFR < 60 mL/min)

• Anemia (hemoglobin <110 g/L)

• Labile INR (TTR <60%)

• Patient Factors

• Diabetes mellitus treated with OHG or insulin

• Current smoker

• CKD (eGFR < 60 mL/min)

• Prior ACS

• Prior stent thrombosis

• Clinical Presentation

• ACS (STEMI, NSTEMI, UA)

• Angiographic factors

• Multi-vessel disease

• Multiple (≥ 3) stents implanted

• Stenting of a bifurcation lesion

• Total stent length > 60 mm

• Left main or proximal LAD stenting

• Chronic occlusion intervention

• Bioabsorbable vascular scaffold

Anticoagulation in the Context

of AF and CAD

Factors that Increase

Risk of Ischemic

Coronary Events

Factors that Increase

Risk of Bleeding

ACS, acute coronary syndrome; CKD, chronic kidney disease; eGFR, estimated glomerular ltration

rate; INR, international normalized ratio; LAD, left anterior descending artery; NSAID, nonsteroidal anti-

inammatory drug; NSTEMI, noneST-elevation myocardial infarction; OHG, oral hypoglycemic agents;

STEMI, ST-elevation myocardial infarction; TTR, Time in Therapeutic Range; UA, unstable angina.

• For patients with AF aged ≥ 65 years or with a CHADS

score ≥ 1 and coronary or arterial vascular disease (peripheral vascular disease or

aortic plaque), we recommend long-term therapy with OAC alone (Strong Recommendation, High-Quality Evidence).

Practical tips:

•

For patients with high-risk clinical or angiographic features for ischemic coronary outcomes who are at low risk of bleeding, some clinicians prefer

a combination of an OAC and single antiplatelet therapy (either aspirin or clopidogrel) in preference to OAC therapy alone.

• Stable coronary artery disease is dened by the absence of acute coronary syndrome for the preceding 12 months.

Values and preferences:

For patients with AF and stable coronary or arterial vascular disease, the CCS AF Guidelines Committee believe that

routine use of combination therapy (an OAC with a single antiplatelet agent) was not justied because of the increased risk of bleeding without

a signicant reduction in ischemic coronary and cerebrovascular thrombotic events.

AF Patients with Stable Coronary Artery Disease or Vascular Disease

Stable vascular disease and AF in patients at high risk of stroke/systemic thromboembolism

Anticoagulation in the Context

of AF and CAD

• For patients with AF aged ≥ 65 years or with a CHADS

score ≥ 1, we recommend an initial regimen of triple antithrombotic therapy (ASA 81

mg daily plus clopidogrel 75 mg/d plus OAC) up to 6 months following PCI (Strong Recommendation, Moderate-Quality Evidence). After ASA

discontinuation, which may occur as early as the day after PCI, we suggest that dual pathway therapy (OAC plus clopidogrel 75 mg/d) be

continued for up to 12 months after PCI (Weak Recommendation, Moderate-Quality Evidence).

Practical tips:

• For some patients < 65 years of age with

CHADS

= 1 at the lower end of the stroke risk spectrum (e.g. isolated hypertension), some clinicians

prefer dual antiplatelet therapy (e.g. aspirin and ticagrelor or prasugrel) in preference to triple therapy (OAC plus dual antiplatelet).

• A PCI is considered high-risk for ischemic coronary outcomes based on the clinical presentation (e.g. ACS), patient characteristics (co-morbid

diabetes mellitus treated with oral hypoglycemics or insulin, chronic kidney disease [eGFR < 60 mL/min], current tobacco use, prior ACS, or prior

stent thrombosis), as well as PCI-related factors (multivessel PCI, multiple [≥ 3] stents implanted, total stent length > 60 mm, complex bifurcation

lesion, chronic total occlusion intervention, and stent type [e.g. bioabsorbable vascular scaffold]).

• All patients should receive ASA 81 mg (or a minimum of 160 mg if ASA-naïve) on the day of the PCI procedure. ASA may be continued as part

of triple antithrombotic therapy for up to 6 months for patients with a high risk of thrombotic coronary events and low risk of bleeding. ASA can be

discontinued as early as the day after PCI for patients with a low risk of thrombotic coronary events and a high risk of bleeding. For patients at

intermediate risk of thrombotic coronary events and intermediate risk of bleeding, ASA can be continued as part of triple antithrombotic therapy

for 1-3 months.

• For patients with AF aged ≥ 65 years or with a CHADS

score ≥ 1, we suggest dual pathway therapy (OAC plus clopidogrel 75 mg/d) for at

least 1 month after BMS implantation and at least 3 months after DES implantation (Weak Recommendation, Moderate-Quality Evidence).

AF Patients Undergoing PCI

AF patients at higher risk of stroke undergoing PCI without high-risk features

AF patients at higher risk of stroke undergoing PCI for ACS or elective PCI with high-risk features

Anticoagulation in the Context

of AF and CAD

• For patients with AF aged ≥ 65 years or with a CHADS

score ≥ 1, we suggest that dual pathway therapy (OAC plus clopidogrel 75 mg/d, rather

than prasugrel or ticagrelor) be given without concomitant ASA for 12 months after ACS (Weak Recommendation, Low-Quality Evidence).

Values and preferences: For patients with AF and type I MI who do not undergo revascularisation, the CCS AF Guidelines Committee places

relatively greater emphasis on the reduction in ischemic coronary and cerebrovascular thrombotic events, rather than the increase in bleeding

observed with combination therapy. When combination therapy is used the preference for clopidogrel rather than ASA is based on the ndings

from the CAPRIE study, where clopidogrel was shown to be superior to ASA (0.5% absolute reduction in composite of vascular death, MI, or

ischemic stroke; P = 0.043), as well as the substantial efcacy and safety data for combination therapy utilizing clopidogrel and OAC (clopidogrel

used in 88% of patients in RE-DUAL PCI and 95% in PIONEER AF-PCI).

AF Patients with Medically Managed Type I Myocardial Infarction

AF patients at higher risk of stroke in association with medically managed type I myocardial infarction

Anticoagulation in the Context

of AF and CAD

Anticoagulation in the Context of Cardioversion

Cardioversion

1. Valvular AF (any duration), or

2. NVAF Duration <12 hours and recent stroke/TIA, or

3. NVA

F Duration 12-48 hours and CHADS

≥2, or

4. NVAF Duration >48 hours

1. Hemodynamically unstable acute AF

, or

2. NVAF Duration <12 hours and no recent stroke/TIA, or

3. NVAF Duration 12-48 hours and CHADS

Therapeutic OAC for ≥3 weeks before cardioversion

CARDIOVERSION

LONG-TERM ANTICOAGULATION BASED

ON THE “CCS ALGORITHM” (CHADS-65)

Hemodynamically unstable acute AF is dened as AF causing hypotension, cardiac ischemia, or pulmonary edema

Alternate: TEE to exclude LA thrombus

Initiate OAC as soon as possible

(preferably prior to cardioversion)

ANTICOAGULATION FOR 4 WEEKS

POST CARDIOVERSION

• We recommend that in addition to appropriate rate-control, most hemodynamically stable patients with AF or AFL for whom elective

electrical or pharmacological cardioversion is planned should receive therapeutic anticoagulation for 3 weeks before cardioversion (Strong

Recommendation, Moderate-Quality Evidence).

• We suggest that, as an alternative to at least 3 weeks of therapeutic anticoagulation prior to cardioversion, transesophageal echocardiography

(TEE) may be employed to exclude cardiac thrombus (Weak Recommendation, Moderate-Quality Evidence).

• We suggest that pharmacological or electrical cardioversion of symptomatic AF or AFL without at least 3 weeks of prior therapeutic

anticoagulation be reserved for patients with the following characteristics (Weak Recommendation, Low-Quality Evidence):

i) patients with non-valvular AF who present with a clear AF onset within 12 hours in the absence of recent stroke or TIA (within 6 months);

ii) patients with non-valvular AF and a CHADS

score < 2 who present after 12 hours but within 48 hours of AF onset.

Practical tip: Non-valvular AF is dened as AF in the absence of mechanical heart valves, rheumatic mitral stenosis, or moderate to severe

nonrheumatic mitral stenosis.

Values and preferences:

This recommendation places a high value on the symptomatic improvement with immediate cardioversion as well

as the reduced risk of peri-cardioversion stroke conferred by a transesophageal echocardiogram demonstrating an absence of intracardiac

thrombus. Lower value is placed on the small risks associated with the TEE.

Anticoagulation in the Context of Cardioversion

Cardioversion

Anticoagulation for at least 3 weeks before elective cardioversion

The use of transesophageal echocardiography as an alternative to anticoagulation prior to cardioversion

Circumstances where cardioversion may be performed without a preceding period of anticoagulation

• We recommend that immediate electrical cardioversion be considered for patients whose recent-onset AF/AFL is the direct cause of instability

with hypotension, acute coronary syndrome, or pulmonary edema (Strong Recommendation, Low-Quality Evidence).

• When a decision has been reached that a patient will be undergoing unplanned cardioversion of AF/AFL, we suggest that therapeutic

anticoagulation therapy be initiated immediately (preferably before cardioversion) with either a NOAC, or with heparin followed by adjusted-

dose warfarin (Weak recommendation, Low-Quality Evidence).

Values and preferences: This recommendation places a high value on immediately addressing instability by attempting cardioversion,

and a lower value on reducing the risk of cardioversion-associated stroke with a period of anticoagulation before cardioversion. Therapeutic

anticoagulation therapy should be initiated as soon as possible.

Anticoagulation in the Context of Cardioversion

Immediate electrical cardioversion for patients who are hemodynamically unstable

Immediate initiation of anticoagulation prior to unplanned cardioversion

Cardioversion

• We suggest that, in the absence of a strong contraindication, all patients undergoing cardioversion of AF/AFL receive at least 4 weeks

of therapeutic anticoagulation (adjusted-dose warfarin or a NOAC) after cardioversion (Weak Recommendation, Low-Quality Evidence).

Thereafter, we recommend that the need for ongoing antithrombotic therapy should be based upon the risk of stroke as determined by the

CCS Algorithm (CHADS-65) (Strong Recommendation, Moderate-Quality Evidence).

Values and preferences: This approach places relatively greater emphasis on the benets of stroke prevention in comparison to the risks

of bleeding with a short course of anticoagulation therapy. Although it may be possible to parse these risks either on the basis of patient

characteristics or the duration of acute AF/AFL, the CCS AF Guidelines Committee at this point has chosen to simplify by recommending

anticoagulation for 1 month after cardioversion for all such patients in the absence of a strong contraindication.

Practical tip:

When oral anticoagulation is to be used for only a short period (< 2 months) current evidence does not substantiate either an efcacy

or safety advantage for use of a NOAC over adjusted-dose warfarin. Nevertheless, the convenience of use of a NOAC over adjusted-dose warfarin

in the pericardioversion period is substantial and the onset of therapeutic anticoagulation is nearly immediate with a NOAC whereas it is delayed in

the case of adjusted-dose warfarin. Accordingly, it is reasonable to use NOAC therapy in the pericardioversion period.

Anticoagulation in the Context of Cardioversion

Anticoagulation for at least 4 weeks post cardioversion

Cardioversion

• We suggest that it is reasonable to prescribe OAC therapy for patients who are aged 65 or older, or with a CHADS

score of ≥ 1 (CHADS-65)

who have episodes of subclinical AF lasting > 24 continuous hours in duration. Additionally, high-risk patients (such as those with a recent

embolic stroke of unknown source) with shorter-lasting episodes might also be considered for OAC therapy (Weak Recommendation, Low-

Quality Evidence).

Investigation and Management of Subclinical AF

Subclinical AF

OAC therapy for highly selected patients with subclinical AF

Notes

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