Transcript Managing Atrial Fibrillation: Taking the Lead with

Atrial Fibrillation When to Ablate, When to
Medicate
John D. Hummel, MD
Professor of internal Medicine
Director, Cardiac Electrophysiology Research
Ross Heart Hospital , Ohio State University
Columbus, Ohio
Atrial Fibrillation
Easily recognized.
Seems to bother healthcare workers as much as patients.
Who’s Problem? Internists cardiologists EP.
The Consequences of AF
Thromboembolism
• Stroke: 4.5 ↑risk
• Microemboli: ↓cognitive
function
• Prothrombotic state
Hospitalizations
• Most common arrhythmia
requiring hospitalization
• 2-3 ↑risk for
hospitalization
• ↓Quality of life
• Palpitations, dyspnea,
fatigue, ↓exercise
tolerance
Impaired
hemodynamics
Mortality
atrial kick
• •2Loss
↑riskofindependent
• Irregular
of
comorbidventricular
CV disease
contractions
• Sudden
death in HF and
• Heart
failure
HCM
• Tachycardia-induced
cardiomyopathy
• AF is an enormous contributor
to the growing cost of medical
care
• Estimated US cost burden:
15.7 billion
Van Gelder IC et al. Europace. 2006;8:943-9; Narayan SM et al. Lancet. 1997;350:943-50.
Wattigney WA et al. Circulation. 2003;108:711-6. Wyse DG et al. Circulation. 2004;109:3089-95.
Learning Objectives
• Review the risk factors for atrial fibrillation.
• Understand the guidelines for
anticoagulation and where there is latitude
for physician decision making.
• Be able to determine when patients should
be evaluated for curative ablation versus
treatment with medical therapy.
DIAGNOSTIC WORKUP
Identify Causes and Risk Factors
•
•
•
•
•
•
•
•
•
•
Minimum Evaluation
History and physical – BP, CV dz, Sleep Apnea
Electrocardiogram – WPW, LVH, MI
Echocardiogram – LVH, LAE, EF, Valve Dz
Labs – TSH, Renal fxn, LFTs
Additional Testing
ETT – CAD, Exercise induced SVT / AF
Holter / Event Monitor – Confirm AF and Sxs
TEE – LA clot
EPS – SVT triggered AF
AHA / ACC / ECS Guidelines
Incidence of AF Based on the Severity of OSA and Obesity
Cumulative frequency of incident atrial fibrillation (AF) during an average 4.7 years
Gami, et al. JACC 2007;49:565-71
The Problem
Incidence of AF Progression
Heart failure
Age
TIA/stroke
COPD
HTN
de Vos CB et al. J Am Coll Cardiol. 2010;55:725-31.
2
1
2
1
1
Goals of Therapy
1. Relieve symptoms
2. Prevent Stroke
3. Prevent Heart Failure
Severity of Stroke with AF
• N = 1061 admitted with acute ischemic
stroke
– 20.2% had AF
• Bedridden state
– With AF
41.2%
– Without AF 23.7%
P < 0.0005
• Odds ratio for bedridden state following
stroke due to AF = 2.23 (P < 0.0005)
• No Difference in Risk with Paroxysmal
vs Persistent AF
Dulli DA et al. Neuroepidemiology. 2003;22:118-23.
Risk Factors for Thromboembolism in AF
CHADS2 Score
High-Risk Factors= 2 points
Previous CVA / TIA / Embolism
Mitral Stenosis
Prosthetic heart valve
Moderate-Risk Factors= 1 point
Age > 75 yrs
HTN
CHF / EF < 35%
DM
Weaker-Risk Factors= no points but add weight
Female
CAD
Thyrotoxicosis
Age 65 – 74 yrs
AHA / ACC / ECS Guidelines 2006
Stroke Risk in AF:
ACP/AAFP Guidelines
CHADS2*
score
Adjusted stroke rate†
(95% CI)
CHADS2
risk level
0
1.9 (1.2–3.0)
Low
ASA
2.8 (2.0–3.8)
Low
ASA /
Warfarin
2
4.0 (3.1–5.1)
Moderate
3
5.9 (4.6–7.3)
Moderate
4
8.5 (6.3–11.1)
High
5
12.5 (8.2–17.5)
High
6
18.2 (10.5–27.4)
High
1
Warfarin
*CHF, hypertension, age ≥75, diabetes, stroke or TIA; †Expected rate of stroke per 100 patient-years
Snow V et al. Ann Intern Med. 2003;139:1009-17.
A score ≥3 indicates “high risk”, and some caution and regular review of
the patient is needed following initiation of any anticoagulant
Camm AJ et al. Eur Heart J. 2010;31:2369-429.
Atrial Fibrillation
Anticoagulation
Novel Oral Anticoagulants
Drug
Dabigatran
Rivaroxaban
Apixaban
Betrixaban
Edoxaban
Mechanism
of action
Thrombin
inhibitor
Factor Xa
inhibitor
Factor Xa
inhibitor
Factor Xa
inhibitor
Factor Xa
inhibitor
T1/2
14-17 hours
5-9 hours
12 hours
19-24 hours
6-12 hours
Regimen
bid
qd, bid
bid
qd
qd
Peak to trough
~7x
12x (qd)
3x-5x
~3x
~3x
Renal
excretion of
absorbed drug
~80%
36%-45%
25%-30%
~15%
35%
Not
substrate
for major
CYPs
CYP3A4
substrate
and
P-glycoprotein
inhibitor
Potential
for drug
interactions
P-glycoprotein
inhibitor
CYP3A4
CYP3A4
substrate
substrate
and
and
P-glycoprotein P-glycoprotein
inhibitor
inhibitor
Usman MH et al. Curr Treat Options Cardiovasc Med. 2008;10:388-97.
Piccini JP et al. Curr Opin Cardiol. 2010;25:312-20.
ACTIVE-A, ACTIVE-W Trials
ACTIVE-W: N = 6706; Warfarin
superior to clopidogrel + ASA;
Trial stopped early*
ACTIVE-A: N = 7554
Median follow-up 3.6 yrs
8
P = 0.01
Outcome / year (%)
7
6 P = 0.0003
6
5
5
4
4
3
P = 0.001
P = 0.53
3
2
2
1
1
0
0
Vascular
event
Stroke
Warfarin
Major
bleeding
Clopidogrel + Aspirin
*Due to clear evidence of superiority of oral
anticoagulation therapy
P < 0.001
P < 0.001
Vascular
event
Stroke
Major
bleeding
Aspirin
ACTIVE Investigators. N Engl J Med. 2009;360:2066-78.
ACTIVE Investigators. Lancet. 2006;367:1903-12.
AF THERAPY
ANTITHROMBOTIC RX
AND
RHYTHM
CONTROL
OR ?
RATE
CONTROL
AFFIRM Trial: Rate vs Rhythm Control
Management Strategy Trial
• Design
– 5-year, randomized, rate control vs. AARx
– Primary endpoint: overall mortality
• Patient population
–
–
–
–
–
–
–
4060 patients with AF and risk factors for stroke
Minimal symptoms
Mean Age = 69 yo
Hx of hypertension: 70.8%
CAD: 38.2%
Enlarged LA: 64.7%
Depressed EF: 26.0%
The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833.
AFFIRM: All-Cause Mortality
30
Rate
Rhythm
25
Mortality, %
20
p=0.078 unadjusted
15
p=0.068 adjusted
10
5
0
0
1
2
3
Rhythm N:
2033
1932
Time (years)
1807
1316
Rate N:
2027
1925
1825
The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833.
1328
4
5
780
255
774
236
Recurrence of AF in Affirm
100 –
Rate Control
80 –
Rhythm Control
Percent
With AF
Recurrence
60 –
40 –
Log rank statistic = 58.62
p < 0.0001
20 –
0–
0
1
2
3
4
5
6
Time (years)
N, Events (%)
Rate control:
563, 3 (0)
167, 383 (69)
98, 440 (80)
42, 472 (87)
10, 481 (92)
2, 484 (95)
Rhythm control:
729, 2 (0)
344, 356 (50)
250, 422 (60)
143, 470 (69)
73, 494 (75)
18, 503 (79)
Raitt, et al. Am H J 2006
Risk of Death in Affirm:
Is Sinus Rhythm the Goal?
AFFIRM: Selected time-dependent covariates associated with
survival
Covariate
P
Hazard ratio*
Sinus rhythm
<0.0001
0.53
0.39–0.72
Warfarin
<0.0001
0.50
0.37–0.69
Digoxin
0.0007
1.42
1.09–1.86
Antiarrhythmic
0.0005
1.49
1.11–2.01
*HR <1.00: Decreased risk of death, HR >1.00: Increased risk of death
AFFIRM Investigators. Circulation. 2004;109:1509-13.
99% CI
RACE II
• Hypothesis: Lenient rate control is not inferior to strict rate
control
• Randomly assigned 614 patients with permanent AF to:
– lenient rate-control strategy (resting heart rate <110 beats per
minute)
– strict rate-control strategy (resting heart rate <80 beats per
minute and heart rate during moderate exercise <110 beats per
minute).
• Primary outcome was a composite of death from
cardiovascular causes, hospitalization for heart failure, and
stroke, systemic embolism, bleeding, and life-threatening
arrhythmic events.
• No Differerence between Lenient and Strict Rate Control
If lenient rate control: check serial echo for declining LV function
Van Gelder, et.al, for the RACE II Investigators NEJM April 15, 2010, No. 15, Vol 362: 1363-1373
APPROACHES TO AF THERAPY
Rate control plus
anticoagulation preferred
•
•
•
•
•
No AF symptoms
Long AF Hx
More SHD
Toxicity Risk
Greater risk of
proarrhythmia
Rhythm control
preferred
•
•
•
•
•
•
Greater AF symptoms
AF compromising LV function
Symptoms despite rate control
Younger age
No or lesser SHD
Rx option of class IC AAD
In anticoagulation candidates, continue anticoagulation indefinitely
Problems with Meds
• Proarrhythmia:
– VT with Flecainide, Propafenone in LVH, CAD,
Decreased EF
– Torsades in Dronedarone, Sotalol, Dofetilide
• Organ Toxicity:
– Amiodarone, procainamide, quinidine
– Organ Toxicity: Lupus, agranulocytosis,
thrombocytopenia, optic neuritis, pulmonary fibrosis,
hepatitis, etc.
ACCF/AHA/HRS 2011 Guidelines Update
Treatment of Atrial Fibrillation
Maintenance of Sinus Rhythm
No (or Minimal)
Heart Disease
Substantial LVH
Dronedarone
Flecainide
Propafenone
Sotalol
No
Amiodarone
Dofetilide
Coronary Artery
Disease
Hypertension
Catheter
Ablation
Dofetilide
Dronedarone
Sotalol
Amiodarone
Dofetilide
Yes
Dronedarone
Flecainide
Propafenone
Sotalol
Amiodarone
Dofetilide
Heart Failure
Catheter
Ablation
Amiodarone
Catheter
Ablation
Amiodarone
Catheter
Ablation
Catheter
Ablation
“In some patients, especially young
individuals with very symptomatic
AF, ablation may be preferred over
years of drug therapy.”*
*Knight BP. HRS Practical Rate and Rhythm Management of Atrial Fibrillation. Updated January 2010. Available at:
http://www.hrsonline.org/ClinicalGuidance/upload/2010_rate-rhythm_guide1.pdf
Prevention of atrial fibrillation by ReninAngiotensin system inhibition
Meta analysis of published clinical trial data on the effects of renin-angiotensin
system (RAS) inhibition for the prevention of atrial fibrillation
A total of 23 randomized controlled trials with 87,048 patients were analyzed.
Overall, RAS inhibition reduced the odds ratio for AF by 33% (p < 0.00001),
but there was substantial heterogeneity among trials.
In primary prevention:
RAS inhibition was effective in patients with heart failure and those with
hypertension and left ventricular hypertrophy
In secondary prevention:
RAS inhibition in addition to antiarrhythmic drugs, including amiodarone, further
reduced the odds for AF recurrence after cardioversion by 45% (p = 0.01) and in
patients on medical therapy by 63% (p <0.00001).
RAS inhibition is an emerging treatment for the primary and secondary prevention
of AF
Schneider MP, et. Al. J Am Coll Cardiol. 2010 May 25;55(21):2299-307
Permanent Atrial Fibrillation Outcome
Study Using Dronedarone on Top of
Standard Therapy (PALLAS)
Dronedarone
N = 1572
n (%)
Placebo
N = 1577
n (%)
Hazard
ratio
P
value
32 (2)
14 (0.9)
2.3
0.009
118 (7.5)
81 (5.1)
1.5
0.006
16 (1)
7 (0.4)
2.3
0.065
3 (0.2)
3 (0.2)
1.0
1
Stroke
17 (1.1)
7 (0.4)
2.4
0.047
Heart Failure hospitalization
34 (2.2)
15 (1)
2.3
0.008
CV death, myocardial infarction,
stroke, systemic embolism*
Death, unplanned CV hospitalization*
Death
Myocardial infarction
Source: http://www.fda.gov/Drugs/DrugSafety/ucm264059.htm
COMET: Effect of Amiodarone on
All-cause Mortality
N = 3029 with chronic HF randomized to carvedilol or
metoprolol Median follow-up 58 months
COMET = Carvedilol or Metoprolol European Trial
Torp-Pedersen C et al. J Card Failure. 2007;13:340-5.
Drug Therapy for Prevention
of Recurrent Atrial Fibrillation
Roy D et al. N Engl J Med. 2000;342:913-20.
ThermoCool: Trial of Ablation vs.
Alternative Antiarrhythmic Medication
N = 167 with paroxysmal AF
• Randomized to catheter
ablation (n = 106) or AAD (n =
61)
• Single procedure
• Mean age 55.7 yrs
• 33.5% women
Wilber DJ et al. JAMA. 2010;303:333-40.
66%
16%
Alternatives to Drug therapy
“Non-Pharmacologic Therapy”
Coumadin – LAA closure (Watchman)
Rate Control – AVN RFA + PCMK
AARx – Adjunctive AFL RFA
AARX – Curative Afib RFA
Watchman
Device
Copyright ©2010 American College of Cardiology Foundation. Restrictions may apply.
Post Surgical LAA Closure
50 pts. MV surgery and LAA ligation
TEE post op 30 pts, 6 days-13 yrs in 20 pts
Incomplete ligation in 18/50 (36%) of pts
No diff. b/w F/U TEE timing, Type of mitral
surgery, operative approach, left atrial size or
degree of MR.
SEC or thrombus in appendage in 9 of 18
(50%) patients with incomplete ligation
4 of these 18 (22%) patients had
thromboembolic events.
Katz et. Al, JACC, 2000
Pacemaker Placement
AVN RF ablation
Complete AVN Ablation
Advantages:
100% efficacy
85% symptomatic improvement
Improved EF (LV remodeling)
Eliminates need for rate control drugs
Disadvantages:
Pacemaker dependant
Risk of LV dysfunction with RV pacing
Some pts still have sx’s
Good Candidates:
Tachy / Brady Syndrome
PCMK in Place – CHF with BiV device
Medication refractory / intolerant
Elderly
Atrial Flutter RFA
Atrial Flutter Circuit
Atrial Flutter Ablation
Approximately 15% of AF patients treated with an AA
will develop AFL
Advantages:
98% efficacy
As primary Rx: RFA more effective than AARx
Increases the success of medical therapy
Disadvantages: Invasive
Good Candidates:
Typical AFL (IVC / TV isthmus)
AARx related AFL
Focal Origin of Atrial
Fibrillation
Hassaiguerre M, NEJM, 1998
• 94% of AF triggers
from Pulmonary
Veins
• “90 – 95% of all
AF is initiated by
PV ectopy”
RA
LA
SVC
17
31
FO
Pulmonary
Veins
6
IVC
CS
11
74 yo medically refractory AF, Echo – Normal
AA Rx - Verapamil, Rythmol, Betapace, Norpace
I
II
III
V1
RSPV
dist
RSPV
prox
LIPV
RA
*
Lasso Catheter
Atrial Fibrillation Ablation
Atrial Shell and Cardiac MRI
Properties of Cryoablation
Hypothermic
Zone
Ablation Zone
(sub-zero)
•
•
•
Removes heat from the tissue
Leads with a wave of hypothermia
Ablates at the point of balloon contact
45 yo with PAF
Conversion of AF to NSR, LSPV with AF
Abl
Lasso
LSPV
CS
A-Fib vs. EP Labs
Current State of Curative
Catheter-Based Ablation at OSU
Procedural Success & Complications
• Total Patients > 2000 (65% Persistent AF)
average procedure 3 hours (2-5)
• Expected success @ 1yr
– ≈ 70% after first procedure
– ≈ 80% after second procedure
• Complications ≈ 1 to 3%
–
–
–
–
–
Tamponade – 0.6%
Pulmonary vein stenosis – 0.6%
TIA / CVA – 0.5%
Esophageal-LA fistula - 0
Groin Bleeding / Hematoma
(Last 200 pts complications < 1.2%)
Phased Rf Catheter Positioning
In Antrum of Right PVs
RSPV
RIPV
II
Pre
Pair 5
Pair 4
Pair 3
Pair 2
Pair 1
Post
II
Pair 5
Pair 4
Pair 3
Pair 2
Pair 1
LIPV RF Ablation
Mitigation of Ablation Risk
• Tamponade: Force sensing catheters
• Esophageal-Atrial Fistula: Esophageal
sensors, Cryoballoon
• CVA/Groin Hematoma: Uninterrupted
Warfarin
• Phrenic nerve Palsy: Phrenic Mapping
FIRM MAP
Animal Rotors/Drivers
Human Rotors
Current State of Curative
Catheter-Based RFA
Who is a good candidate?
Symptomatic / Frequent AF
Limited Heart Dz
LA < 5.5cm
No MS / Rheumatic Dz
Younger Patients
Medically Refractory / Intolerant
(Ablation now second line therapy)
Atrial Fibrillation: Ablation vs Drug Rx.
Ablation
70% success
PV stenosis
AE fistula
TIA/CVA
Drug Rx.
40% success
Proarrhythmia
End Organ Toxicity
No Free Lunch
Torsades
AE fistula
PV stenosis
Current State of Curative
Catheter-Based RFA
Who is a good candidate?
Symptomatic / Frequent AF
Limited Heart Dz
LA < 5.5cm
No MS / Rheumatic Dz
Younger Patients
Medically Refractory / Intolerant
(Ablation now second line therapy)
SAFE-T: Sinus Rhythm vs AF – Increase
in Maximal Exercise Duration
100
Increase in duration (mean)
90
P = 0.01
P = 0.02
80
70
60
50
40
30
20
10
0
8 weeks
Singh SN et al. J Am Coll Cardiol. 2006;48:721-30.
1 year
Sinus rhythm
Atrial fibrillation
Catheter Ablation vs. Surgical
Ablation
• 2/3 patients failed catheter ablation, 1/3 HTN and
LAE
• Freedom from left atrial arrhythmia (30 seconds)
without antiarrhythmic drugs after 12 months:
– 36.5% for CA
– 65.6% for SA (P=0.0022)
• Safety end point of significant adverse events
– 16% for Catheter Ablation
– 35% for Surgical Ablation (P=0.027)
Statins in Prevention of AF (1st Episode
or AF Recurrence)
Study
or subcategory
MIRACL
Tveit
Dernellis
ARMYDA 3
Chello
Ozaydin
Total (95% CI)
Statin
n/N
Control
n/M
93/1539
18/51
14/40
35/101
2/20
3/24
96/1548
17/51
36/40
56/99
5/20
11/24
1775
Favors
treatment
Favors
control
1782
Total events: 165 (Statin), 221 (Control)
0.1 0.2 0.5 1
2
5 10
Odds ratio (random); 95% CI
Not assessed in this meta-analysis:
Degree of LDL-C; Statin dose
Test for heterogeneity: Chi2 = 29.47, df = 5 (P < 0.0001), I2 = 83.0%
Test for overall effect: Z = 2.35 (P = 0.02)
Fauchier L et al.
J Am Coll Cardiol. 2008;51:828-35.
AF TREATMENT GOALS
• AF is rarely life-threatening and is
typically recurrent
• Treatment goals in symptomatic pts
–  frequency of recurrences
–  duration of recurrences
–  severity of recurrences
• Minimize risk of tachycardia induced
cardiomyopathy
• Safety is primary concern
AFFIRM
Functional Status Substudy
• Lower NYHA functional class in patients in
sinus rhythm
• 6 min walk tests – 94 feet longer in Rhythm
Control group (P = 0.049)
Chung MK et al. J Am Coll Cardiol. 2005;46:1891-9.
Types of Atrial Fibrillation
• First diagnosed AF
– Categorized as 1st presentation, regardless of AF
duration or presence/severity of AF symptoms
• Paroxysmal AF
– Self-terminating, usually 48 hours
• Persistent AF
– Lasts >7 days or requires termination by cardioversion
• Long-standing persistent AF
– Lasts ≥1 year
• Permanent AF
– Presence of arrhythmia is accepted by patient (and
physician)
Camm AJ et al. Eur Heart J. 2010;31:2369-429.
Mortality: AF vs Sinus
Rhythm
70
60
AF
SR
P = 0.04
P = NS
P = 0.001
50
P  0.001
40
P = NS
30
20
n=427
n=795
10
n=234
n=6517
n=390
0
V-HeFT
(Carson)
Mahoney
SOLVD
(Dries)
Middlekauff
Crijns
Carson PE et al. Circulation. 1993;87(suppl VI):VI-102-VI-110; Dries DL et al. J Am Coll
Cardiol. 1998;32:695-703; Crijns HJ et al. Eur Heart J. 2000;21:1238-45; Middlekauff HR
et al. Circulation. 1991;84:40-8; Mahoney P et al. Am J Cardiol. 1999;83:1544-7.
Permanent Atrial Fibrillation Outcome
Study Using Dronedarone on Top of
Standard Therapy (PALLAS)
• A randomized, double-blind, placebo controlled,
parallel group trial for assessing the clinical
benefit of dronedarone 400 mg bid on top of
standard therapy in patients with permanent AF
and additional risk factors
• Eligible patients were ≥65 years, in permanent
AF (defined by the presence of AF/atrial flutter
for ≥6 months prior to randomization without
plans to restore sinus rhythm), with ≥1
additional CV risk criterion
Source: http://www.fda.gov/Drugs/DrugSafety/ucm264059.htm
Permanent Atrial Fibrillation Outcome
Study Using Dronedarone on Top of
Standard Therapy (PALLAS)
• Co-primary endpoints:
– Major cardiovascular events (stroke, systemic
arterial embolism, myocardial infarction or
cardiovascular death), or
– Unplanned cardiovascular hospitalization or death
from any cause
• In July 2011, the data monitoring committee reviewed
the preliminary data and concluded that there was a
significant excess of CV events in the dronedarone
group for both co-primary endpoints as well as other
CV events. As a result, the PALLAS study was
stopped.
Source: http://www.fda.gov/Drugs/DrugSafety/ucm264059.htm
FDA Response Since
PALLAS
"At this time, patients taking Multaq
should talk to their healthcare
professional about whether they should
continue to take Multaq for nonpermanent atrial fibrillation. Patients
should not stop taking Multaq without
talking to a healthcare professional.
Healthcare professionals should not
prescribe Multaq to patients with
permanent atrial fibrillation."
Source: http://www.fda.gov/Drugs/DrugSafety/ucm264059.htm
DIAMOND – Evidence for Survival
Benefit of Sinus Rhythm
Probability of survival
Probability of survival
Survival rates of patients treated with dofetilide or placebo by SR
conversion status
Dofetilide group
1.0
SR
Not SR
0.8
0.6
0.4
0.2
0.0
0
6
12
18
1.0
24
30
36
42
48
24
30
Time (months)
36
42
48
Placebo group
0.8
0.6
0.4
0.2
0.0
0
6
12
18
Pedersen OD et al.Circulation. 2001;104:292-6.
Catheter Ablation vs Antiarrhythmic
Drugs for AF: Early Studies
The APAF Study
The A4 Study
Jais P. et al. Circulation. 2008;118:2498-505.
Pappone C et al. J Am Coll Cardiol. 2006;48:2340-7.
Early studies limited by small study populations, variable entry criteria and definitions
of success, and were conducted in single or limited number of centers
Dabigatran vs. Warfarin
Noninferiority trial randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive:
1. Fixed doses of dabigatran — 110 mg or 150 mg twice daily in a blinded fashion
2. Adjusted-dose warfarin in an unblinded fashion
The median duration of the follow-up period was 2.0 years.
The primary outcome was stroke or systemic embolism.
Results
Primary outcome
1.69% per year in the warfarin group
1.53% per year in the group that received 110 mg of dabigatran (P<0.001 for noninferiority)
1.11% per year in the group that received 150 mg of dabigatran ( P<0.001 for superiority)
Major bleeding
3.36% per year in the warfarin group
2.71% per year in the group receiving 110 mg of dabigatran (P=0.003)
3.11% per year in the group receiving 150 mg of dabigatran (P=0.31).
Hemorrhagic stroke
0.38% per year in the warfarin group
0.12% per year with 110 mg of dabigatran (P<0.001)
0.10% per year with 150 mg of dabigatran (P<0.001).
Mortality rate
4.13% per year in the warfarin group
3.75% per year with 110 mg of dabigatran (P=0.13)
3.64% per year with 150 mg of dabigatran (P=0.051).
Conclusions
Dabigatran 110 mg had rates of stroke and systemic embolism similar to warfarin with less major hemorrhage.
Dabigatran 150 mg had lower rates of stroke and systemic embolism but similar rates of major hemorrhage.
Stuart J. Connolly and the RE-LY Steering Committee and Investigators NEJM Sept 17, 2009, No. 12, Vol 361: 1139-1151
PABA-CHF: Study Design
Prospective, randomized, controlled trial
N = 81 with symptomatic, drug-resistant AF; LVEF ≤40%; NYHA Class II or III HF
Pulmonary-vein isolation
(n = 41)
Atrioventricular-node ablation with
biventricular pacing (n = 40)
Primary outcome: Composite of ejection fraction, 6-minute walk distance,
and Minnesota Living with Heart Failure score at 6 months
PABA-CHF = Pulmonary Vein Antrum Isolation versus AV Node Ablation with Bi-Ventricular
Pacing for Treatment of Atrial Fibrillation in Patients with Congestive Heart Failure
Khan MN et al. N Engl J Med. 2008;359:1778-85.
PABA-CHF: Composite Primary
Endpoints at 6 Months
Randomized trial of NYHA Class II or III CHF & EF <40% to PVI or
AVN + BiV
6-Minute walk
AVN + BiV
PVI
340
320
Ejection fraction
P < 0.001
37
300
280
AVN + BiV
260
0
0
3
Months
6
MLHF score*
100
P < 0.001
80
Score*
PVI
Ejection fraction (%)
Distance (m)
360
PVI
35
33
P < 0.001
31
29
27
AVN + BiV
25
60
0
40
0
20
0
0
Months
6
*↓Score = ↑QoL
Khan MN et al. N Engl J Med. 2008;359:1778-85.
3
Months
6
Wann LS et al. Circulation. 2011;8:157-76.