Transcript INR 2.0-3.0 - MCE Conferences

ATRIAL FIBRILLATION
Nora Goldschlager, M.D.
MACP, FACC, FAHA, FHRS
Cardiology – San Francisco General Hospital
UCSF
Disclosures: None
Individuals with AF only
(millions)
INCREASING PREVALENCE OF AF
8
6
All
4
Men
2
Women
0
2005
2015
2025
2035
2045
Year
Naccarelli et al AJC 2009;104:15334
Reuters database, US Census Bureau Projected Estimates
INCIDENCE
• Occurs in ≥ 2% of population
(more than 5 million pts in US;
projected >10 million by 2050)
• Prevalence increases with age
1% in people > 60
5 - 6% of people > 65
14% of people > 80
• Associated with > 100,000 strokes / yr
• Develops in 10 - 30% of pts with
LV dysfunction; is a predictor of
mortality (1 - 3x)
• RR for death 1.5 (men) and 1.9 (women)
CONSEQUENCES OF AF IN THE US:
US DATABASE ANALYSIS
350,000 hospitalizations/yr
7 million office visits/yr
542,000 ED visits/yr
$6.42 billion annually
Coyne et al Circulation 2004; 110:III - 826
Zimetbaum, Circulation 2005; 111:3141
CLASSIFICATION
Types
• Paroxysmal
• Persistent
• Permanent
– Self-terminating
– Requires cardioversion
to restore sinus rhythm
– Complete inability to
maintain sinus rhythm
Etiologies
• Rheumatic
• Nonrheumatic
• Lone
ASYMPTOMATIC ATRIAL FIBRILLATION
• Incidence 20 - 50%
• Most asymptomatic pts have chronic AF
• Up to 50% of pts with paroxysmal AF have
no symptoms (pacemaker stored data)
• Occurs in up to 20% of pts with no AF
history (ICD stored data)
• Is present in up to 30% of pts presenting
with stroke without AF history
AF IN HEART FAILURE
Risk of AF in systolic dysfunction
• Men 4.5x
• Women 5.9x
• Whites 38%
• AA 20%
• NYHA I-II 10%
IV 50%
AF in diastolic dysfunction
• Prevalence ~ 10%
• Risk related to degree of
diastolic dysfunction (echo) hazard ratio 3.3  5.3
Prevalence of AF (%)
NEW YORK HEART ASSOCIATION
FUNCTIONAL CLASS
60
I
II-III
40
20
0
Maisel, Stevenson
AJC 2003;91:2-8
III-IV
IV
DOES AF INCREASE CHF MORTALITY?
Framingham Study: evaluated temporal effect of
development of AF or CHF on mortality
Mortality HR (95% Cl)
Patients with AF
Add CHF
Patients with CHF
Add AF
Men
Women
2.7 (1.9 - 3.7)
3.1 (2.2 - 4.2)
1.6 (1.2 - 2.1)
2.7 (2.0 - 3.6)
Wang et al. Circulation 2003;107(23)2920-2925
AF AND RACE IN
PATIENTS HOSPITALIZED WITH CHF Dx
• Incidence:
AA (n = 223) - 20%
Caucasian - 38%
• AA: younger (67 vs 74, p  .001)
HT (87% vs 78%, p  .01)
Prior CHF (79% vs 71%, p  .01)
Less CAD Dx
• AA lower odds of AF (49%) after adjustment
for EF, age, gender, meds, DM, CHF etiology
Ruo et al JACC 2004; 43:429
EPOCH study patients N = 1373; 37% with AF
Kaiser database
AF IN WOMEN
• Although risk is higher in men, 53% of all AF
pts are women
• Women with CHF have 14x risk of AF,
8.5x risk in men
• Suggestion that embolism in women > men
• More sx, higher VR
• Higher proarrhythmia risk with AARx
Cumulative survival
EFFECT ON MORTALITY OF AF IN
HEMODIALYSIS PTS (INDEPENDENT OF EF)
1.2
.8
71.3 %
.4
19.2 % AF
N=26
SR
N=164
0
0
10
20
Vazquez et al
30
Mos
AJC 10.1.03
40
N = 190
50
AF free survival (%)
INFLAMMATION AS A RISK FACTOR FOR AF
100
Pts w/CRP level < median
(1.92 mg/liter)
95
90
c
Pts w/CRP level > median
(1.92 mg/liter)
85
80
0
0
1
2
3
4
Yrs
5
6
Aviles et al Circulation 2003;108:3006 N = 5806
Cardiovascular Health Study (5% AF at baseline)
7
Cumulative frequency
of AF (%)
OBSTRUCTIVE SLEEP APNEA
AND INCIDENT AF
15
OSA
10
5
No OSA
0
0
2
4
6
8
Years
JACC 2007;49:565
10
12
14
POTENTIAL MECHANISMS OF
ASSOCIATION OF AF AND OSA
• Diastolic dysfunction with increase in LA size
• Negative intrathoracic pressure fluctuations
leading to transmural pressure changes
and wall stress
• Ion channel changes
– stretch-sensitive
– catacholamine-sensitive (apnea-related
increase)
– vagal tone increase (end-apneic periods)
• Systemic inflammation associated with OSA
• Hypoxemia
• Hypercarbia
• sympathetic drive
AF DURING ACUTE MI
Incidence:
11% on entry
11% during hospitalization
Correlations: Age
Anterior MI
Killip IV
Prior MI
CHF*
Outcomes:
Higher death rates (indep. predictor)
- In hospital* 25% (vs 16% no AF)
- 30 days*
29% (vs 19%)
- 1 yr
48% (vs 33%)
Reinfarction
* Higher in AF developing during MI
Rathmore et al, Circulation 3.00, N = 106,780 medicare pts > 65 yo ((79)
AF AND SUDDEN CARDIAC
DEATH MORTALITY
• In the AVID Registry, AF present in 23% of patients
AF independent risk factor of SCD mortality (RR=1.20; P=.02)
• In MUSTT and MADIT II, AF was the second largest
independent risk factor for SCD
• CASS Registry: AF independent risk factor for SCD
• V-HeFT I and V-HeFT II: no correlation between
mortality and AF
The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators.
N Engl J Med. 1997;337:1576 Wyse et al. J Interv Card
Electrophysiol. 2001;5:267 Zareba. Presented at NASPE 23rd
Scientific Session; May 2002 Cameron el al. Am J Cardiol. 1988;61:714
MANAGEMENT OPTIONS IN AF
Ventricular rate control
CA++ -blockers
-blockers
Digoxin
AVN ablation
Restoration of NSR
Electrical conversion
Antiarrhythmic drugs
Maintenance of NSR
Antiarrhythmic drugs
Dual chamber pacing
Atrial overdrive pacing
Dual site atrial pacing
Atrial septal pacing
AF ablation
REASONS TO PERFORM EARLY
RESTORATION OF NSR IN PTS WITH AF
• The longer the AF duration, the higher energy
levels (transthoracic and internal) required
for cardioversion
• Repeated atrial burst pacing leads to longer
episodes of AF, eventuating in chronic AF
(goats)
• The longer the AF episodes, the greater the
atrial EP and histologic pathology
ANTIARRHYTHMIC DRUGS
TO MAINTAIN SINUS RHYTHM
Agent
• None
• Class 1A, and Sotalol
• Class 1C (propafenone,
flecainide)
• Dofetilide
• Amiodarone
• Dronedarone
% of pts in
sinus rhythm at 1yr
25%
50%
50 - 60%
~ 60%
70 - 80%
about 60%
Failure to convert AF to NSR does not mean that
drug will not maintain NSR once it is achieved
EVALUTION OF AARx THERAPY
TO MAINTAIN SR
• Time to 1st AF recurrence (should not be
sole criterion of drug failure)
• Frequency of AF recurrences
• Duration of AF recurrences
• Symptoms during AF recurrences
AF: POST CONVERSION SR vs AF
AND SERUM ALDOSTERONE LEVELS
200
24 h before CV
24 h after CV
Serum 150
Aldo
(pg/ml) 100
50
0
SR
maintained
Wozakowska-Kaplon et al
AF
recurrence
PACE 2010; 33:561
EURIDIS/ADONIS
• Patient enrollment: 1237 patients
• Inclusion criteria: Presence of paroxysmal
or persistent AF or AFL, with ≥ 1 documented
episode in the 3 months prior to enrollment,
and in normal sinus rhythm for at least 1 hour
• Primary endpoint: Time from randomization
to first AF/AFL recurrence
• Study medication: Dronedarone 400 mg BID
or placebo for 12 months
• Results: Dronedarone prolonged time to
first recurrence of AF/AFL
Combined RR reduction: 25%
Absolute RR reduction: 11% at 12 months
N Engl J Med 2007;357:987-999
DRONEDARONE*
EURIDIS AND ADONIS TRIALS
•
•
•
•
•
•
*
incidence of 1st (symptomatic) AF
recurrence
VR during AF recurrences
hospitalization or death rates
(also ATHENA trial)
No substantial effect on QT interval
(? Atrial selectivity)
Low Torsades de pointes risk
Avoid in HF patients (ANDROMEDA study)
Multiple ion-channel blockade; half-life 1-2 days
DRONEDARONE FOR
SR MAINTENANCE IN AF AND FLUTTER
Cumulative
incidence (%)
80
Placebo
60
Dronedarone
40
Hazard ratio, 0.75
P < 0.01
20
0
0
60
120
270
360
112
307
90
262
Days
No. at risk
Placebo
409
Dronedarone 828
180
192
450
156
389
Singh et al NEJM 2007; 357:987
133
347
ATHENA: OVERVIEW - 1
•
Objective
A multicenter, multinational, doubleblind, randomized placebo-controlled
study of dronedarone in 4628 patients
with a recent history of AF/AFL who were
in sinus rhythm or who were to be
converted to sinus rhythm to assess the
efficacy of dronedarone 400 mg bid for
the prevention of cardiovascular
hospitalization or death from any cause
Hohnloser SH et al J Cardiovasc Electrophysiol. 2008;19:69-73
Hohnloser SH et al N Engl J Med 2009;260:668-678
ATHENA: OVERVIEW - 2
• Patients representative of general AF
population
– History of paroxysmal or persistent AF/AFL
– Aged ≥ 75 years with or without additional
risk factors
– Aged ≥ 69 years and ≥ 1 risk factor
(HT, DM prior CVA/TIA, LA diameter ≥ 50
mm, LVEF < 40)
Hohnloser SH et al J Cardiovasc Electrophysiol. 2008;19:69-73:
N Engl J Med 2009;260:668-678
ATHENA: OVERVIEW - 3
• Primary endpoint: Time to first CV
hospitalization or death from any cause
• Secondary endpoints: All-cause mortality
CV hospitalization
Hohnloser SH et al J Cardiovasc Electrophysiol. 2008;19:69-73;
N Engl J Med 2009;260:668-678
ATHENA: SUMMARY
• Dronedarone significantly prolongs time
to first CV hospitalization in patients with
paroxysmal or persistent AF and
associated CV risk factors
• Reduction in CV hospitalization mainly due
to admissions for AF
• The 24% reduction in cardiovascular
hospitalization or death from any cause was
generally consistent in all subgroups
based on baseline chracteristics or
medications
ATHENA: DRONEDARONE AND
CV EVENTS IN AF
Cumulative
incidence (%)
Primary outcome (1st hospitalization
due to CV events or death)
50
Placebo
25
Dronedarone
P < 0.001
0
0
6
12
24
30
1072
1177
385
403
3
2
Mos
No. at risk
Placebo
2327
Dronedarone 2301
18
1858
1963
1625
1776
Hohnloser et al NEJM 2009; 300:668
ATHENA: DRONEDARONE AND
CV EVENTS IN AF
Cumulative
incidence (%)
Death from CV causes
Placebo
5.0
P < 0.03
2.5
Dronedarone
0
0
6
12
24
30
1629
1593
636
615
7
4
Mos
No. at risk
Placebo
2327
Dronedarone 2301
Hohnloser et al
18
2290
2274
2250
2240
NEJM 2009; 300:668
ANDROMEDA: OVERVIEW -1
• Designed to evaluate dronedarone,
400 mg BID, on all-cause death or
hospitalization for worsening heart failure
• Enrolled 627 of 1000 patients (310 and 317
in the dronedarone and placebo groups,
respectively)
• Patients had relatively severe heart failure
and had been hospitalized, or referred to a
speciality heart failure clinic for worsening
symptoms
Kφber L: et al N Engl J Med 2008;358:2678-2687
ANDROMEDA: OVERVIEW - 2
• 38% of subjects had a history of AF/AFL
and 25% had AF/AFL at enrollment
• Primary composite endpoint : all-cause
mortality or hospitalization for heart
failure
• Trial terminated because of a two-fold
increase in mortality in dronedarone
group
Kφber L: et al N Engl J Med 2008;358:2678-2687
ACC / AHA / ESC GUIDELINES:
RISK-STRATIFIED ANTITHROMBOTIC Rx
Risk factors: HF, LV EF  0.35, Hx HT
Age < 60, no HD
Age < 60 + HD,
no risk factors
Age > 60
Age  60, DM or CAD
Any age + risk factors
or thyrotoxicosis
Fuster et al
Rx
ASA (325 mg/d or no Rx)
ASA (325 mg/d)
Warfarin (INR 2.0 - 3.0)
Warfarin (INR 2.0 - 3.0) 
low dose ASA (class IIb)
Warfarin (INR 2.0 - 3.0)
Eur Heart J. 2001;22:1852-1923
ACC / AHA / ESC GUIDELINES:
RISK-STRATIFIED ANTITHROMBOTIC Rx
Risk factors: HF, LV EF  0.35, Hx HT
Age  75 (pts c risk
bleed - esp )
Rx
Warfarin (INR -2.0)
Rheumatic HD, prosthetic Warfarin (INR 2.5-3.5
heart valves, prior
or higher may
thromboembolism,
be appropriate)
persistent atrial
thrombus on TEE
Fuster et al
Eur Heart J 2001;22:1852-1923
RISK STRATIFICATION FOR
ANTICOAGULATION IN AF:
CHADS2 Score
Points
•
•
•
•
•
Congestive heart failure
Hypertension
Age 75 years or older
Diabetes mellitus
Stroke or TIA history
Gage BF et al JAMA 285: 2864-2870; 2001
1
1
1
1
2
ANTICOAGULATION RECOMMENDATIONS
BY CHADS2 SCORE
• CHADS2 0
– Low risk (0.5%/yr)
– ECASA 325 mg qd
• CHADS2 1-2
– Intermediate risk (1.5-2.5%/yr)
– Warfarin (INR 2.0-3.0) > ECASA 325 mg qd
• CHADS2  3
– High risk (5.3-6.9%/yr)
– Warfarin (INR 2.0-3.0) unless contraindicated
VITAMIN K ANTAGONISTS IN AF
• Reduce stroke by 38%, compared
to aspirin
• Recommended in high risk
patients with AF
• Only 40-50% of ideal patients
receive VKA in Western countries
– Many patients considered
unsuitable
– Due to poor INR control,
concern about bleeding
– Patient preference
HYPOTHESIS OF ACTIVE A
In patients with AF, unsuitable for VKA
therapy, addition of clopidogrel to aspirin will
reduce the risk of major vascular events, at
acceptable risk of major bleeding
ACTIVE A - STUDY TREATMENT
• All patients received aspirin at a
recommended daily dose of
75-100 mgs
• Patients were randomized, double
blind, to clopidogrel, 75 mg per
day, or matching placebo
OUTCOMES AND STATISTICAL POWER
• Primary outcome was a composite of major
vascular events:
– Stroke, myocardial infarction, non-CNS
systemic embolism or vascular death
• Secondary outcomes
– Stroke
– Major hemorrhage
• 7500 patients planned to achieve 88% power
to detect 15% reduction in primary outcome
(1600 events)
STUDY CONDUCT
• 33 Countries, 580 centers
• 7554 patients enrolled between
June 2003 and May 2006
• Final follow up in November 2008
– Median follow up 3.6 years
– Follow up was complete in
99.4% of patients
Primary Outcome (Stroke, MI, non-
0.3
H R=0.89 (0.81-0.98) p=0.014
0.2
Placebo+Aspirin
0.1
C lopidogrel+Aspirin
0.0
Cumulative Hazard Rates
0.4
CNS Systemic Embolism, Vascular Death)
0
No. at Risk
C+ A 3772
ASA 3782
1
2
3
4
3456
3426
3180
3103
2522
2460
1179
1156
Years
0.15
0.10
H R=0.72 (0.62-0.83) p=0.00002
0.05
Placebo+Aspirin
C lopidogrel+Aspirin
0.0
Cumulative Hazard Rates
Stroke
0
No. at Risk
C+ A 3772
ASA 3782
1
2
3
4
3491
3458
3229
3155
2570
2517
1203
1186
Years
0.02 0.03 0.04 0.05
HR=0.78 (0.59-1.03) p=0.077
Placebo+Aspirin
0.01
Clopidogrel+Aspirin
0.0
Cumulative Hazard Rates
Myocardial Infarction
0
No. at Risk
C+ A 3772
ASA 3782
1
2
3
4
3529
3521
3297
3259
2635
2632
1264
1265
Years
BENEFITS AND RISKS:
COMPARED TO WARFARIN
Warfarin
versus
Aspirin
Clopidogrel &
Aspirin
versus
Aspirin
Meta-analysis*
(RRR)
ACTIVE A
(RRR)
Reduction in stroke
- 38%
-28%
Increase in intra-cranial
bleed
+128%
+87%
Increase in extra-cranial
bleed
+70%
+51%
Effects
*Hart RC et al. Meta-analysis: Antithrombotic therapy to prevent stroke in
patients who have non-valvular AF . Ann Intern Med 2007: 146: 857-67
RE-LY: A Non-inferiority Trial
Atrial fibrillation
≥1 Risk Factor
Absence of contra-indications
951 centers in 44 countries
Blinded Event Adjudication.
R
Open
Warfarin
adjusted
(INR 2.0-3.0)
N=6000
Blinded
Dabigatran
Etexilate
110 mg BID
N=6000
Dabigatran
Etexilate
150 mg BID
N=6000
RE-LY: A Non-inferiority Trial
Atrial fibrillation
≥1 Risk Factor
Absence of contra-indications
951 centers in 44 countries
Blinded Event Adjudication.
R
Open
Warfarin
adjusted
(INR 2.0-3.0)
N=6000
Blinded
Dabigatran
Etexilate
110 mg BID
N=6000
Dabigatran
Etexilate
150 mg BID
N=6000
0.06
D 150 mg vs.
Warfarin
RR
=1.11
95% CI = 0.89-1.40
P
= 0.35
RR
= 0.76
95% CI = 0.60-0.98
P
= 0.03
0.04
D 110 mg vs.
Warfarin
Dabigatran110
0.02
Warfarin
Dabigatran150
0.0
Cumulative Hazard Rates
0.08
Ischemic/Unspecified
Stroke
0
0.5
1.0
1.5
Years of Follow-up
2.0
2.5
0.04
Hemorrhagic Stroke
RR
=0.26
95% CI =0.14-0.49
P
<0.001
0.02
0.03
RR
= 0.31
95% CI =0.17-0.56
P
<0.001
D 150 mg vs.
Warfarin
0.01
Warfarin
Dabigatran110
Dabigatran150
0.0
Cumulative Hazard Rates
D 110 mg vs.
Warfarin
0
0.5
1.0
1.5
Years of Follow-up
2.0
2.5
RATIONALE:
RATE CONTROL vs RHYTHM CONTROL
Rhythm Control
• Loss of AV synchrony may produce sx
• Prevents remodeling effects of AF
• May play a role in stroke prevention
Rate Control
• Anti-arrhythmic therapy is only
~ 60% effective long-term
• Pro-arrhythmia and other side-effects
• Many symptoms are relieved with
adequate control of rate
ADVANTAGES OF RATE CONTROL
VS RHYTHM CONTROL - 1
• Rate control (with anticoagulation):
- No or few Sx of AF
- Greater degree of structural heart
disease (e.g., requiring amiodarone)
- Adverse response to AA Rx
- Greater risk of proarrhythmia
EF
Gender
QT
ADVANTAGES OF RATE CONTROL
VS RHYTHM CONTROL - 2
• Rhythm control:
- Sx with AF that impact QOL
- Sx despite adequate rate control
- Young age
- No or little structural heart disease
- No or immediate need for AA Rx with
significant side effect profile
- Contraindication to anticoagulation
- 1st AF episode
AF FOLLOWUP INVESTIGATION OF
RHYTHM MANAGEMENT (AFFIRM) TRIAL
Inclusion criteria:
• > 65 y.o. or other risk factor for stroke or
death*; > 6 hrs AF in past 6 mos
• FU 3.5 y
• Rate control group 80/min rest, < 110/min
with 6 min walk
• End points
1º - overall mortality
2º - composite: death, stroke, bleed,
cardiac arrest
* HT 70%, CAD 38%, LAE 65%, prior TIA, CHF 24%,
avg EF 55%
NEJM 12.5.02
N = 4060 enrolled, 7401 screened
Cumulative
mortality
(%)
AF FOLLOWUP INVESTIGATION OF
RHYTHM MANAGEMENT (AFFIRM) TRIAL
p = 0.08
20
Rhythm control
10
Rate control
0
Deaths:
No. (%)
0
Rhythm control 0
Rate control
0
NEJM 12.5.02
1
80 (4)
78 (4)
2
3
Years
175 (9)
148 (7)
4
5
257 (13) 314 (18) 352 (24)
210 (11) 275 (16) 306 (21)
AFFIRM: ADVERSE EVENTS
Rate
control
Rhythm
control
79 (5.7%)
84 (7.3%)
INR > 2.0
24 (30%)
18 (22%)
INR < 2.0
28 (35%)
17 (20%)
Not taking
warfarin
26 (33%)
48 (58%)
AF at time
of event
45 (69%)
25 (36%)
Ischemic stroke
AFFIRM: LIMITATIONS
• Enrolled older, high risk pts
• Chronic or paroxysmal AF could be enrolled;
PAF pts in rate control arm may have had
NSR at times (52% of pts in rate control arm
were in NSR at randomization); some pts in
rhythm control arm likely had AF at times
• AF recurrences and durations not known
over time in rhythm control group; periods
of NSR not known in rate control group
AFFIRM IMPLICATIONS I
• Studied patients presumably required
long-term Rx and had risk factors for stroke
• Coumadin should be continued in patients
who are thought to be rhythm controlled
• AA drugs are not an alternative to
coumadin
AFFIRM IMPLICATIONS II
• Rate control carries no higher mortality or
lower functional benefit over rhythm
control
• Did not answer the question of whether SR
is better than AF with rate control
• Compared current pharmacologic strategies
– Imperfect rhythm control
– Incomplete monitoring of rhythm (single
ECG at FU; no Holter data)
• Decision to rate or rhythm control should be
based on symptoms
POTENTIAL NEW MANAGEMENT
STRATEGIES IN AF
AND PTS AT RISK FOR AF
ACE inhibitors
ARBs
Antiinflammatory agents
ASA
Statins
Fish oil
Freedom from AF
EFFECT OF ENALAPRIL ON AF INCIDENCE* IN
PTS WITH LV DYSFUNCTION (SOLVD STUDY)
Enalapril n = 186 (5%)
1.0
.75
Placebo n = 188 (24%)
.50
Risk reduction 19%
0
0
1
2
3
Time (yrs)
4
* Most episodes were paroxysmal
Vermes et al Circulation 2003;107:2926-2931
AF developed in 55 / 374
5
POSSIBLE EFFECT ON ATRIAL REMODELING IN
AF BY AT RECEPTOR BLOCKERS*
.0
Amio + Irbesartan
Pts free
.9
150-300 mg/d
of AF
.8
recurrences
.7
Amio 400 mg
(%)
.6
.5
0 60 120 180 240 300 360
FU (days):
* Effects: Reduction of fibrosis
Prevention/reduction of apoptosis
Less shortening of atrial refractory period
during rapid atrial rates
Madrid et al
Circulation 2002;106:331
N = 154
Proportion of pts
with first event (%)
HT AND NEW-ONSET AF (LIFE STUDY)
8
HR: 0.67, p<0.001
6
Losartan
Atenolol
4
2
0
0
12
24
36
Months
Wachtell et al JACC 2005; 45:712
N = 9193, 150 Losartan, 221 Atenolol
48
60
HT AND AF (LIFE STUDY):
SUMMARY OF RESULTS
• Results of AF outcomes are independent
of BP reduction
• AF increases cardiac morbidity/mortality
in HT with LVH
• Losartan reduces AF recurrence risk in
pts with AF history
• Losartan reduces incidence of new-onset
AF (33%)
• Potential mechanisms
- LV and LA hypertrophy regression
- Atrial remodeling reversal
- Reduction in atrial fibrosis
Probability of
1st AF recurrence
VALSARTAN AND 1st AF RECURRENCE
.
6
Placebo
Valsartan
.4
.2
P = 0. 83
0
0
No. at risk
Placebo
720
Valsartan 722
Gissi - AF
N = 1,442 CVD, DM or LAE;
LVEF > 40% in > 90%;
Lone AF ~ 10%;
70% on AARx
2
4
6
8
10
12
Mos since randomization
520
524
454
465
NEJM 2009; 360:16
407
423
377
383
344
356
254
260
STATIN USE AND IN-HOSPITAL
ARRHYTHMIAS IN ACS
Prior statin
Patients (%)
10
7.4
8
6
6.9
No prior statin
8.2
5.5
4.3
3.2
4
2
0
VT/VFCA
AF/flutter
Hospital
death
Vedre et al, GRACE registry 1999-2007
AJC 2009;104:1613
N=64, 679, 27% statin use
NEW-ONSET AF AFTER HOSPITAL ADMISSION
FOR CAD STRATIFIED BY STATIN USE WITHIN
ONE MONTH OF HOSPITAL DISCHARGE
Incidence of
New AF (%)
100
5 y:
10y:
No Statin
38.3%
58.0%
50
Adjusted HR 0.90 ± 0.03 P = 0.0006
0
0
At risk:
Statin
8,450
No statin 20,638
Kulik et al
Statin
32.6%
51.2%
60
120
Months post-discharge
AJC 2010; 105:1655
2,247
6,711
146
841
Medicare database 1995-2004
N = 29,088
META-ANALYSIS OF RCTS: EFFECT OF
STATINS ON AF
All AF
Statin n/M Control n/M
MIRACL
Tveit
Dernellis
ARMYDA3
Chelio
Ozaydin
93/1539
18/51
14/40
35/101
2/20
3/24
OR 95% Cl
96/1548
17/51
36/40
56/99
5/20
11/24
0.97
1.09
0.06
0.41
0.33
0.17
P = .02
0.39
.02
Rx
Fauchier et al
OR
JACC 2008; 51:828
1 2
5
Control
Favors
META-ANALYSIS OF RCTS: EFFECT OF
STATINS ON AF
Primary prevention (post-operative or new onset AF)
Statin n/M Control n/M
MIRACL 1 25/1421
ARMYDA 3 35/101
Chelio
2/20
OR 95% Cl
23/1440
56/99
5/20
1.10
0.41
0.33
P = NS
0.60
.02
Rx
Fauchier et al
OR
JACC 2008; 51:828
1 2
5
Control
Favors
META-ANALYSIS OF RCTS: EFFECT OF
STATINS ON AF
AF Recurrence (FU ≥ 6 wks)
Statin n/N Control n/N
MIRACL 2
Tveit
Dernellis
Ozaydin
68/118
18/51
14/40
3/24
OR 95% Cl
73/108
17/51
36/40
11/24
0.65
1.09
0.06
0.17
P = .06
0.33
.02
Rx
Fauchier et al
OR
JACC 2008; 51:828
1 2
5
Control
Favors
POTENTIAL CANDIDATES FOR CURATIVE
AF ABLATION:
PATIENT CHARACTERISTICS
• Frequent paroxysmal AF
(not persistent)
• Frequent isolated PACs on monitoring
• Lone AF
• Younger patient and minimal HD
• Focal AF
REVIEW OF ABLATION STUDIES
• Most patients:
Young (55 y.o.)
Preserved LVEF (~ 60%)
LA diameter ~ 5 cm
• 1º end point usually AF recurrence
(assessed by various means)
• No RCTs on stroke risk, death
• Short FU
Teresawa et al Annals Int Med 2009;151:191
PREDICTORS OF LACK OF
SUCCESS OF AF ABLATION
• Persistent AF
• LA volume (>130 cc) (echo and CT)
• LA diameter >5cm (TEE)
• Low or absent voltage of atrial
electrograms (indicating scar)
LESS CONSISTENT PREDICTORS
OF FAILED AF ABLATION
•
•
•
•
•
LA diameter (TTE)
Hypertension
Age, gender
AF duration
Structural heart disease including
valvular disease
• LVEF
• DM
• CAD
LEFT ATRIAL APPENDAGE OCCLUSION
• Device (WATCHMAN) must be left in the
left atrium
• Alternative: Minimally invasive epicardial
ablation
• NOT ALL AF ARISES FROM THE LEFT
ATRIAL APPENDAGE! Up to 10% of emboli
will not be approached by this method
• May have best use in patients who are
refractory to warfarin