Update in Direct-acting Oral Anti-Coagulants
(DOACs, NOACs)
►
Faculty: Paul Dorian, MD, FRCPC
Director, Division of Cardiology, St. Michael's Hospital
Professor, University of Toronto
►
Relationships with commercial interests:
 Advisory Board/Grants/Clinical Trials: Bayer, BMS,
Pfizer, BI
Disclosure of Commercial Support
► This
program has received financial support
from Bristol-Myers Squibb Canada, ManthaMed,
and Mazola Canada in the form of an
unrestricted educational grant
Potential for conflict(s) of interest:
► Bristol Meyers Squibb, Bayer, Pfizer, and
Boehringer Ingelheim developed a product
that may be discussed in this program.
Mitigating Potential Bias
►
►
►
All the recommendations involving clinical medicine are
based on evidence that is accepted within the profession
Recommendations conform to the generally accepted
standards.
Potential bias will be mitigated by presenting a full range
of products that can be used in this therapeutic area
Step wise systematic approach to AF
(1)
• Is there documentation of AF ( at least 30sec)?
• If there are symptoms, are symptoms
correlated with AF recordings?
• What is the AF pattern? ( paroxysmal,
persistent )
• Are there reversible/treatable causes?
Step wise systematic approach to AF
(2)
• How much do the symptoms affect quality of life?
( this is NOT the same as are there symptoms ?)
• What are the patient’s values and preferences
with respect to treatment? ( shared decision
making)
• Is the patient educated about the causes,
contributing factors, self management ? ( eg
coffee, stress do NOT cause AF; exercise is NOT
contraindicated ; ETOH in moderation is allowed;
it is NOT necessary to go to ER with AF ,except
rarely; AF does NOT cause MI …)
Step wise systematic approach to AF
(3)
• Consider if rate or rhythm control are
indicated ( QOL primarily)
• Assess risks and benefits of each
• Establish treatment goals explicitly
• Plan course of action with patient ( Plan A,
Plan B, Plan C. etc…)
• Explain stroke prevention is separate and
apart as a risk assessment and strategy,
unrelated to symptoms
The most common pathogenesis of AF
Obesity
Sleep apnoea
Hypertension
Congestive heart failure
Atrial fibrosis/inflammation
AF
Most common overlooked
causes/contributing factors to AF
• Undiagnosed/inadequately treated
hypertension
• Obesity/sleep apnea
• Lifelong competitive exercise
• Episodic alcohol excess
Poorly Controlled Blood Pressure is Independently
Associated with a 50% Higher Risk of in Patients with Atrial
Fibrillation: ARISTOTLE Trial
*Poorly controlled blood pressure is defined as SBP >140 mm Hg and/or DBP >90 mm Hg at any point during the trial using the average of 2
most recent blood pressure measurements for each time point.
Stroke or systemic embolism endpoint adjusted by age, region, weight, diabetes, moderate valvular disease, prior stroke/TIA/systemic
embolism, type of atrial fibrillation and prior VKA use. Death from any cause, cardiovascular death, and myocardial infarction adjusted for by
age, sex, region, weight, moderate valvular disease, left bundle branch block, history of myocardial infarction, prior stroke/TIA/systemic
embolism, anemia, smoking status, prior VKA use, NYHA class, CHADS2 score and renal function. Bleeding safety outcomes were adjusted by
age, sex, region, coronary artery disease, prior myocardial infarction, history of bleeding, anemia, CHADS2 score, and renal function.
Rao et al. Presented as a poster at the ACC 2014
- Moderate Endurance Training Decreases the Risk for Lone Atrial
Fibrillation. Results of the FUTURE study
Calvo et al HRS 2014
Baseline risk
in sedentary persons
Vigorous exercise eg
approx 1 hr. 3X/wk
for 20 years increases risk
Moderate exercise reduces risk
regression analysis associated height (OR 1.06 P=0.03), waist circumference (OR 1.06
[95% CI 1.02 - 1.11], P<0.01), OSA (OR 5.04 P=0.01), and cumulative heavy sport
activity of more than 2000h with an increased risk of AF (OR 4.52 [95% CI 1.88 11.34], P<0.001).
Azarbal F JAMA 2014 Aug 20
Alcohol ( current vs never vs prior) and
strenuous exercise
did not increase the risk of incident AF
12 yr f/up
10,000/80,000 with AF
Exercise attenuates the effect of obesity in promoting AF
No diet will remove all the fat
from your body because the brain
is entirely fat. Without a brain,
you might look good, but all could
do is run for public office.
George Bernard Shaw
Quality of life scores in AF patients compared to
historical controls
SF-36
Subscales
(range 0-100)
AF
Patients
(n=152)
CHF
Patients
(n=216)
Post MI
Patients
(n=69)
General health
54±21
47±24**
59±19*
Physical functioning
68±27
48±31**
70±26
Vitality
47±21
44±24
58±19**
Mental health
68±18
75±21**
76±16**
Social functioning
71±28
71±33
85±21**
Higher scores represent better quality of life
**p<0.01, *p<0.05, compared to AF patients
Dorian P et al. J Am Coll Cardiol 2000;36:1303‒9
Rate and rhythm control
Rate control is a reasonable first strategy,
primarily to slow resting rate < 100/min, and
improve QOL . There is no advantage in
slower rates unless symptoms warrant
Rhythm control is useful only if quality of life
is improved
This applies to cardioversion, antiarrhythmic
drugs, and ablation
Olesen B et al, BMJ 2011;342:d124
Stroke/SE rates/100 pt yrs ( no OAC)
ALL pts. are CHADS 0 or 1
Age 65-74 stroke rates
The “CCS Algorithm” for OAC Therapy in AF
Age 65
YES
OAC*
NO
Prior Stroke/SE/TIA or
Hypertension
or
Heart failure
or
Diabetes Mellitus
YES
OAC*
(CHADS2 risk factors)
**may require lower dosing
NO
CAD or
Arterial vascular disease
Consider and modify (if possible)
all factors influencing risk of
bleeding on OAC (hypertension,
antiplatelet drugs, NSAIDs,
excessive alcohol, labile INRs)
and specifically bleeding risks for
NOACs (low eGFR, age ≥ 75, low
body weight)**
YES
ASA
(coronary, aortic, peripheral)
NO
No
Antithrombotic
* We suggest that a NOAC be used in preference
to warfarin for non-valvular AF.
Warfarin:High Efficacy
Stroke
Death
67%
26%
Effect of VKA compared to placebo
1. Hart RG et al. Ann Intern Med. 2007;146:857-867;
2. CCS 2012 AF Guidelines Can J Cardiol . 2012; 28:125-136
In theory, theory is as good
as practice.
In practice, it isn’t
Yogi Berra
What is the problem ?
• Initiation of Warfarin is associated with an
early increased risk of major hemorrhage
• Initiation of warfarin in patients newly
diagnosed with AF increases stroke rates in
the short run ( 2-4 weeks
• Doctors still ( 2002-2012) don’t like to use
warfarin
• More than ½ of pts stop warfarin within a year
Initiation of Warfarin is associated with an
early increased risk of hemorrhage
First 30 d rate
of
hemorrhage
is
11.8%/person
year
Overall rate of
hemorrhage
3.8%/person
year
Gomes et al. CMAJ 2013; 185: E121 -
Granger, C.B. et al. EHJ (2012) 33 (Abstract Supplement), 685-686 and ESC 2012 oral presentation available at 5
Granger, C.B. et al. EHJ (2012) 33 (Abstract Supplement), 685-686 and ESC 2012 oral presentation available at
http://spo.escardio.org/eslides/view.aspx?eevtid=54&fp=4045
For medical non-promotional reactive use only
Risks of stopping Apixaban: lessons from Aristotle
Granger, C.B. et al. EHJ (2012) 33 (Abstract Supplement), 685-686 and ESC 2012 oral presentation available at
http://spo.escardio.org/eslides/view.aspx?eevtid=54&fp=4045
For medical non-promotional reactive use only
Persistence rates in newly diagnosed nonvalvular
AF patients
• Large US administrative database to study the persistence of AF patients on
dabigatran vs warfarin
• Patients beginning with dabigatran had significantly higher persistence
than patients initiated on warfarin (63% vs 39%, P<0.001)
Warfarin persistence rates
< 60 day Rx interruption
Zalesak M et al. Circ Cardiovasc Qual Outcomes 2013;6:567–74
New oral anticoagulants in patients with atrial
fibrillation: a meta-analysis of phase III trials
Major bleeding
Dabigatran 150 mg b.i.d.
Rivaroxaban 20 mg o.d.
Apixaban 5 mg b.i.d.
Edoxaban 60 mg o.d.
Combined
Note: Important differences between the treatments, patient demographics and trial
characteristics that might affect study outcomes were not accounted for in the metaanalysis.
Ruff CT et al. Lancet 2013 Dec 3; doi: 10.1016/S0140-6736(13)62343-0
New oral anticoagulants in patients with atrial
fibrillation: a meta-analysis of phase III trials
Stroke or systemic embolic events
Dabigatran 150 mg b.i.d.
Rivaroxaban 20 mg o.d.
Apixaban 5 mg b.i.d.
Edoxaban 60 mg o.d.
Combined
Note: Important differences between the treatments, patient demographics and trial
characteristics that might affect study outcomes were not accounted for in the meta-analysis.
Ruff CT et al. Lancet 2013 Dec 3; doi: 10.1016/S0140-6736(13)62343-0
ROCKET AF – Bleeding Analysis
Rivaroxaban
(N=7111)
Parameter
Warfarin
(N=7125)
Hazard ratio
(95% CI)
n (% per year) n (% per year)
Principal safety
endpoint
1475 (14.9)
1449 (14.5)
1.03 (0.96,1.11)
Major bleeding
395 (3.6)
386 (3.4)
1.04 (0.90,1.20)
Hemoglobin drop
(≥2 g/dl)
305 (2.8)
254 (2.3)
1.22 (1.03,1.44)*
Transfusion
183 (1.6)
149 (1.3)
1.25 (1.01,1.55)*
Critical organ
bleeding
91 (0.8)
133 (1.2)
0.69 (0.53,0.91)*
55 (0.5)
84 (0.7)
0.67 (0.47,0.93)*
27 (0.2)
55 (0.5)
0.50 (0.31,0.79)*
1185 (11.8)
1151 (11.4)
1.04 (0.96,1.13)
Intracranial
hemorrhage
Fatal bleeding
Non-major clinically
relevant bleeding
Major bleeding from gastrointestinal site (upper, lower and rectal):
rivaroxaban = 224 events (3.2%); warfarin = 154 events (2.2%); p<0.001*
Safety population – as-treated analysis; *statistically significant
Patel et al. N Engl J Med. 2011 Sep 8;365(10):883-91
Hazard ratio
and 95% CIs
0.2
0.5 1
2
5
Favors
Favors
rivaroxaban
warfarin
ARISTOTLE
Bleeding outcomes
Outcome
Primary safety outcome:
ISTH major bleeding*
Apixaban
(N=9088)
Warfarin
(N=9052)
Event Rate Event Rate
(%/yr)
(%/yr)
HR (95% CI)
P Value
2.13
3.09
0.69 (0.60, 0.80)
<0.001
Intracranial
0.33
0.80
0.42 (0.30, 0.58)
<0.001
Other location
1.79
2.27
0.79 (0.68, 0.93)
0.004
Gastrointestinal
0.76
0.86
0.89 (0.70, 1.15)
0.37
Major or clinically relevant
non-major bleeding
4.07
6.01
0.68 (0.61, 0.75)
<0.001
GUSTO severe bleeding
0.52
1.13
0.46 (0.35, 0.60)
<0.001
TIMI major bleeding
0.96
1.69
0.57 (0.46, 0.70)
<0.001
Any bleeding
18.1
25.8
0.71 (0.68, 0.75)
<0.001
*Part of hierarchical sequence preserving a type I error
Adapted from Granger CG et al. N Engl J Med 2011;10.1056/NEJMoa1107039. NEJM.org 28 August 2011
Life threatening bleeding
RR 0.67 (95% CI: 0.54–0.82)
p<0.001 (sup)
RR 0.80 (95% CI: 0.66–0.98)
2.00
p=0.03 (sup)
RRR
20%
RRR
33%
1.50
1.85
% per year
1.49
1.24
1.00
0.50
0.00
D110 mg BID
147 / 6,015
Connolly SJ., et al. N Engl J Med 2009; 361:1139-1151.
D150 mg BID
179 / 6,076
Warfarin
218 / 6,022
Outcomes after Major Bleeding:
Dabigatran vs. Warfarin
13.0%
p=0.052
8.4%
• N=1034 with 1121 major bleeds in 5 phase
III trials comparing dabigatran with warfarin
in 27419 patients
• Major bleeds with dabigatran treated more
frequently with blood transfusions (61% vs.
42%), less frequently with plasma (20% vs.
31%)
• Patients who experienced a bleed had a
shorter ICU stay if previously treated with
dabigatran vs. warfarin (mean 1.6 vs. 2.7
nights, p=0.01)
Majeed et al. Circulation. 2013; 128: 2325-2332
R
Piccini J et al. European
Heart Journal Advance
W
HR R vs W
Major Bleeding in Patients with Atrial Fibrillation Receiving Apixaban or
Warfarin in the
ARISTOTLE Trial: Predictors, Characteristics, and Clinical Outcomes
Hylek et al JACC epub ahead of print Feb 2014 10.1016/j.jacc.2014
Novel Oral Anticoagulants as
Compared to Warfarin
APIXABAN1
DABIGATRAN 1102
DABIGATRAN 1502
RIVAROXABAN3
VS. WARFARIN
VS. WARFARIN
VS. WARFARIN
VS. WARFARIN
RR (95% CI)
P
RR (95% CI)
P
RR (95% CI)
P
RR (95% CI)
P
Stroke/SE
0.79
(0.66−0.95)
= 0.01
0.91
(0.74−1.11)
0.34
0.66
(0.53−0.82)
< 0.001
0.88
(0.75−1.03)
0.12
Major Bleed
0.69
(0.60−0.80)
< 0.001
0.80
(0.69−0.93)
0.003
0.93
(0.81−1.07)
0.31
1.04
(0.90−1.20)
0.58
Intra Cranial Bleed
0.42
(0.30−0.58)
< 0.001
0.31
(0.20−0.47)
< 0.001
0.40
(0.27−0.60)
< 0.001
0.67
(0.47−0.93)
0.02
GI bleeding
0.89
(0.70-1.15)
0.37
1.10
(0.86-1.41)
0.43
1.5
(1.19-1.89)
<0.001
1.61
(1.30-1.99)
<0.001
All cause Death
0.89
(0.80−0.99)
0.047
0.91
(0.80−1.03)
0.13
0.88
(0.77−1.00)
0.051
0.92
(0.82−1.03)
0.15
No head-to-head trials between dabigatran, apixaban and rivaroxaban have been conducted, therefore comparative efficacy
and safety have not been established.
1. Granger et al., NEJM 2011; 365: 981-992
2. Connolly et al., NEJM 2009; 361: 1139-1151
3. Patel et al., NEJM 2011; 365: 883-891
35
“Applying the Guidelines”
STEP 1
Why does this patient have AF?
Manage treatable factors
STEP 2
What is the AF related quality of life?
If SAF≥2, consider modifying treatment/strategy
If SAF≥3, consider referral
STEP 3
What is the stroke and bleeding risk?
Most patients will require OAC
Educate to ensure adherence and safety
STEP 4
What is the follow-up strategy?
•Are there modifiable factors
that contribute to symptoms?
•Sleep apnea, Hypertension
•ETOH excess, Smoking, Obesity
•Are symptoms and rhythm
correlated?
•Are treatment and follow-up
affecting QOL?
•Address modifiable bleeding risk factors
to optimize stroke prevention
•Recommend OAC when age > 65 OR
CHADS ≥ 1
•Monitor QOL, adherence, renal function
Consider referral if pt. still symptomatic after rate co
Representative Cases You See In
Practice
My brother in law
•
•
•
•
•
•
•
Retired schoolteacher, aged 66 ( and a good guy)
Hypertensive, well controlled on an ARB
No other meds/illnesses
Doesn’t exercise much, BMI 30
Goes to Cancun on an all inclusive( you figure it out)
3 mo later, routine GP visit :irregular pulse
ECG: A Fib, otherwise normal, rate 78/min
NOW What?
Dr YD, Age 42, Family Practitioner
Last evening he was out celebrating the
marriage of his receptionist and consumed
about 12 ounces of Johnny Walker Black
label. He went home by taxi, slept poorly
and realized this morning about 6:00 am that
his heart rate was rapid and pulse irregular.
He has a mild bitemporal headache and is
driven to the ED by his wife.
He has been well, no known hypertension, DM, heart
disease, TIA/stroke and no known arrhythmias although
he does have mild palpitations from time to time. No
COPD or asthma.
In ED: no chest pain, mild SOB, slightly sweaty.
HR 140, irregularly irregular, BP 140/90, JVD 4 cm, Chest
clear. ECG shows AF, rate 140.
Dr YD, Age 42, Family Practitioner
How will you manage his rhythm?
1. Electrical cardioversion (150-200 j) in ED as soon as it
can be done.
2. IV metoprolol 5 mg, repeated Q 5 min up to 3 times if
rate remains above 110. Home on po metoprolol 50-100
mg bid if AF persists.
3. IV metoprolol 5 mg, repeated Q 5 min up to 3 times if
rate remains above 110. Add propofenone 450 mg po
about 10-15 minutes after first dose of metoprolol if AF
persists.
4. IV metoprolol 5 mg, repeated Q 5 min up to 3 times if
rate remains above 110. Electrical cardioversion if AF
persists.
5. Digoxin 0.25 mg IV, repeat at 1 hr intervals up to 4
doses if AF persists.
Dr YD, Age 42, Family Practitioner
How will reduce his risk of stroke if you decide to
cardiovert him?
1. IV LMWH or a NOAC po about 1 hr prior to any
cardioversion attempt.
2. IV LMWH or a NOAC po about 1 hr prior to electrical
cardioversion, but not required for pharmacologic
cardio version.
3. No anticoagulant required pre cardioversion attempt.
4. Start dabigatran 150 mg bid and have him return for
cardioversion after 3 weeks of dabigatran.
Dr YD, Age 42, Family Practitioner
How will reduce his risk of stroke post discharge from
ED?
1. If AF persists, he requires maintenance ASA 81 mg
daily at least until follow-up at 1 month.
2. Whether AF persists or resolves, he requires
maintenance ASA 81 mg at least until follow-up at 1
month.
3. If AF persists, he requires maintenance OAC at least
until follow-up at 1 month.
4. Whether AF persists or resolves, he requires
maintenance OAC at least until follow-up at 1 month.
5. Whether AF persists or resolves he requires no
maintenance antithrombotic therapy.
Dr YD, Age 42, Family Practitioner
How will reduce his risk of stroke post discharge from
ED?
1. If AF persists, he requires maintenance ASA 81 mg
daily at least until follow-up at 1 month.
2. Whether AF persists or resolves, he requires
maintenance ASA 81 mg at least until follow-up at 1
month.
3. If AF persists, he requires maintenance OAC at least
until follow-up at 1 month.
4. Whether AF persists or resolves, he requires
maintenance OAC at least until follow-up at 1 month.
5. Whether AF persists or resolves he requires no
maintenance antithrombotic therapy.
A guidelines based approach to AF management
• A 77 yr old lady has hypertension, otherwise well
• Lives alone, has a dog
• On Ramipril 10 mg and bisoprolol 5 mg a day for
hypertension
• 5 ft 5 in, 190lbs.
• Comes to the office for routine BP follow-up
P Dorian CCC 2014
www.ccs.ca
Atrial Fibrillation Guidelines
• Pulse rate 85/min, irregular
• BP 145/95 , repeated X 3
• No murmurs , no signs CHF
• Says she feels well
• On closer questioning, she walks the dog around the
block; she used to walk to the park, 2-3 kms away,
but “no longer feels like it”
• EKG shows AF, otherwise normal, rate 88/min
www.ccs.ca
Atrial Fibrillation Guidelines
What next?
Why does she have AF?
1. Thyroid
2. Hypertension
3. Sleep apnea
4. Ethanol
www.ccs.ca
Atrial Fibrillation Guidelines
What next?
What are the risks and benefits of rhythm control?
www.ccs.ca
Atrial Fibrillation Guidelines
History
Establish Severity (including impact on QOL)
Identify Etiology
Identify reversible causes (hyperthyroidism, ventricular pacing,
SVT, exercise)
Identify factors whose treatment could reduce recurrent AF or
improve overall prognosis (i.e. hypertension, sleep apnea, left
ventricular dysfunction)
Identify potential triggers (i.e. alcohol, intensive aerobic training)
Identify potentially heritable causes of AF (particularly in lone AF)
Determine thromboembolic risk (e.g. CHADS2 Score)
Determine bleeding risk to guide appropriate antithrombotic
therapy
Review prior pharmacologic therapy for AF, for efficacy and
adverse effects
www.ccs.ca
Atrial Fibrillation Guidelines
Establish AF Severity
Use to Guide Therapeutic Approach
CCS
SAF Score
Impact on QOL
0
Asymptomatic
1
Minimal effect on QOL
2
Minor effect of QOL
3
Moderate effect on QOL
4
Severe effect on QOL
Dorian et al Can J Cardiol 2006;22:383-386
www.ccs.ca
Atrial Fibrillation Guidelines
• SAF class 2-3 on detailed discussion
• Choices:
– increase beta blocker
– attempt to restore sinus rhythm
• CHADS = 2 (CHADSVaSC 4)
• OAC for 3-4 weeks
• Electrical Cardioversion
www.ccs.ca
Atrial Fibrillation Guidelines
Rhythm Management - Recommendations
• We recommend that an AV blocking agent should be used in patients with AF or AFL being treated with a class I
antiarrhythmic drug (eg, propafenone or flecainide) in the absence of advanced AV node disease (Strong
Recommendation, Low Quality Evidence).
• We recommend electrical or pharmacologic cardioversion for restoration of sinus rhythm in patients with AF or AFL
who are selected for rhythm-control therapy and are unlikely to convert spontaneously (Strong Recommendation, Low
Quality Evidence).
• We recommend pre-treatment with antiarrhythmic drugs prior to electrical cardioversion in patients who have had AF
recurrence post cardioversion without antiarrhythmic drug pre-treatment (Strong Recommendation, Moderate Quality
Evidence).
• We suggest that patients requiring pacing for the treatment of symptomatic bradycardia secondary to sinus node
dysfunction, atrial or dual-chamber pacing be generally used for the prevention of AF (Conditional Recommendation,
High Quality Evidence).
• We suggest that, in patients with intact AV conduction, pacemakers be programmed to minimize ventricular pacing for
prevention of AF (Conditional Recommendation, Moderate Quality Evidence).
www.ccs.ca
Atrial Fibrillation Guidelines
• How likely is cardioversion to be successful?
• ( distinguish “success” with IRAF from “failure”)
• If sinus rhythm restored , how likely is AF to recur?
• What can be done to prevent recurrence?
• HT control, ETOH reduction if excessive, sleep
apnea treatment if appropriate
www.ccs.ca
Atrial Fibrillation Guidelines
How do we tell if rhythm control is justified?
• Assess QOL without knowing the rhythm or doing
an EKG
• eg QOL improves post CV, and worsens again with
recurrence, vs
• No better, or better, but AF recurs without
symptoms
www.ccs.ca
Atrial Fibrillation Guidelines
Rate vs Rhythm Control for Patients with Symptomatic AF
SYMPTOMATIC AF
ATTEMPT RATE CONTROL
Beta-blocker
Calcium channel blocker
Special circumstances in
which to consider early
rhythm control:
Highly symptomatic
Multiple recurrences
Extreme impairment in QOL
Arrhythmia-induced
cardiomyopathy
SYMPTOMS RESOLVE
YES
NO
CONTINUE RATE
CONTROL
MODIFY RATE CONTROL - CONSIDER RHYTHM CONTROL
Paroxysmal AF
Low burden
recurrence
High burden
recurrence
Pill in pocket
antiarrhythmic
therapy
Maintenance
antiarrhythmic
therapy
Persistent AF
Consider cardioversion
Symptoms
improve,
but AF recurs
Catheter
ablation
Canadian Cardiovascular Society AF guidelines
CJC Oct 2014
Symptoms improve,
and patient maintains
sinus rhythm
Observe. If AF
recurs, determine if
symptomatic
Rate and Rhythm Management
Symptoms
don’t change
in sinus
rhythm and
AF recurs
Overview of Rhythm Management
Rhythm Control Choices
Normal Systolic Function
No Hx of CHF
Dronedarone+
Flecainide*
Propafenone*
Sotalol#
Rhythm Control Choices
Hx of CHF or Left Ventricular
Systolic Dysfunction
EF > 35%
EF ≤ 35%
Amiodarone
Sotalol**
Amiodarone
Catheter
Ablation
Amiodarone
Catheter Ablation
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, age > 65 yr, taking diuretics)
www.ccs.ca
Atrial Fibrillation Guidelines
** Sotalol should be used with caution with EF 35-40% and those at risk
for torsades de pointes VT (e.g. female, age > 65 yr, taking diuretics)
Dr. Fred Brown, a GP colleague,
asks for your advice about
Mr. MB, Age 67
Heart “skipping beats” and “racing”, especially
on exertion –2 weeks prior to GP visit
•Previously well, active, no significant
limitations
•No hypertension, DM, CHF, no meds
•HR 100 irreg, BP 135/85
•HS normal, no murmurs or gallops, JVP just
visible at 45°
Dr. Fred Brown, a GP colleague,
asks for your advice about
Mr. MB, Age 67 (cont’d)
•Hgb 145, Glucose 5.4, Cr 1.0 (eGFR 110)
•EKG – AF 95/min
•Echo – unremarkable (LA 4.0, LV 5.0, EF 55%,
no LVH)
Dr. Brown started him on atenolol 50 mg qam
and symptoms are much improved
Mr. MB, Age 67 yr, 1 week post atenolol 50 mg qam
3. How would you treat him to reduce his risk of
stroke?
1. No antithrombotic therapy ?
2. ASA 81 mg/day ?
3. OAC ?
Mr. MB, Age 67
BUT, within the group of patients with
CHADS2 = 0 (annual stroke risk 1.9%):
• Data from Danish epidemiological
studies indicate the following annual
risk of stroke:
Age 65-74: 2.13%
Vascular disease: 1.40%
Age < 65, no vascular disease:0.7%
3. How would you treat him to reduce his
risk of stroke?
1. No antithrombotic therapy ? Incorrect. Given his
2.1% annual risk of stroke it would be wise to
prescribe antithrombotic therapy.
1. ASA 81 mg/day ? Incorrect. Probably inadequate
protection. His stroke risk would be reduced by
about 20%, with an annual risk of major bleeding of
about 0.5%.
1. OAC ? Correct! Best choice. OAC recommended by
CCS Guidelines.
In theory, theory is a good as practice.
In practice, it isn’t.
• 64 yr old obstetrician
• Symptomatic AF, fails rhythm control,
scheduled for AF ablation; CHADSVaSC=0
• Postpones ablation , on ASA 81 mg /d
• Sudden onset aphasia, confusion
• Basilar artery clot evacuated by
neuroradiologist
• Visit 2 mo later : “on warfarin”
In theory, theory is a good as practice.
In practice, it isn’t.
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•
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He has recovered 95%
He has 5 first degree relatives as MDs
He has 4 physicians looking after him
He is happy with the status quo
What do you do?
In theory, theory is a good as practice.
In practice, it isn’t.
1) no action required
2) check his recent INRs
3) Recommend switching to Dabigatran
4) recommend switching to Rivaroxaban
5) Recommend switching to Apixaban
In theory, theory is a good as practice.
In practice, it isn’t.
• His last 4 INRs:
• 1.5, 1.6, 1.5, 1.7
• What now?
What stroke prevention do you
recommend?
1) Reinforce better warfarin management
2) Dabigatran 150 mg BID
3) Dabigatran 110 mg BID
4) Rivaroxaban 20 mg OD
5) Apixaban 5 mg BID
In the clinic
• An 82 yr old man is referred for “A Fib”
• Slight dyspnea , otherwise well
• Prior CAD, stents a year ago , LV slightly
depressed EF 45% , hypertensive
• On ACEI, beta blocker ( metoprolol 12.5 mg
BID), ASA
• Heart rate 75/min
• ECG: A Fib
In the clinic
• On closer questioning : 2 weeks ago walked
the golf course , now cannot walk one hole
• On exertion, HR 150/min
• Now what?
In the clinic
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Dyspnea due to diastolic dysfunction
NT-BNP shows heart failure
BB increased; dabigatran started (110 BID)
Cardioversion scheduled
St Michael’s AF clinic
FAX 416-864 5348
NP: Jenn Cruz
NP : Vimy Barnard