Can we stop anticoagulant after successful catheter ablation?

Kazuo Matsumoto, MD. PhD.Cardiology Department of International Mecial Center,

Saitama Medical UniversityHigashi-matsuyama Medcial Association Hospital

2016/6/17

What to Expect After Catheter Ablation of AFib?

To resolve problems caused by AFib.

High Mortality

Heart Failure

Stroke

And patient would like to stop medicines ,

especially anticoagulants・・・・・!?

Symptoms

2016/6/17

Guidelines of ESC/AHA (1, 2) recommendation :

Anticoagulation should be sustained for minimum of 3 months after ablation of AF , and further evaluation of persistent anticoagulant therapy should be considered based on individual patient’s risk factors for stroke

(Class Ⅱa , level ｏｆ evidence C)

1, Camm AJ et al:Europace 2010;12:1360-1420.

2, Fuster V et al: Jam Coll Cardol 2011;57:e101-98.

What are individual patient’s risk factors for stroke ?

2016/6/17

BleedingRisk Thrombosis

Risk

Thrombosis Risk vs. Bleeding Risk

Maintenance of

Anticoagulants

HAS-BLED ≧ 3

Recurrence of AFib

CHADS2 ≧ 2

Atrial fibrillation ablation patients have long-term stroke rates

similar to patients without atrial fibrillation

regardless of CHADS2 score

T. JaredBunch,MD ,John D.Day,MD et al:Heart Rhythm2013;10:1272–1277

A total of 37,908 patients were included in this study.

①patients with AF who had undergone ablation,

n=4212,

②patients with AF who did not undergo ablation

n=16,848 (age-/sex- matched controls)

③patients without a history of AF.

n=16,848 (age-/sex- matched controls)

OBJECTIVE ： To determine if ablation of atrial fibrillation

reduces stroke rates in all risk groups.

The ablation approach, postablation anti-coagulation strategy, and follow-up

schedule were determined by the patient’s electrophysiologist and not

by a system-wide protocol.

Kaplan-Meier survival curves of freedom from stroke based on

AF status and treatment and CHADS2 risk score.E

vent-

Fre

e S

urv

ival (

Str

oke E

vent)

AF ablation of each CHDAS2 risk ( 0-1,2.3,more than 4) is alomost the same

progonosis as no AF and superior prognosis to AF no ablation(p<0.0001).

(days)

*

CHADS2 0-1

*CHADS2 2-3

*

CHADS2 >=4

*

AF NO ablation

vs

No AF

AF ablation

vs

No AF

Increased risk versus no AF

1.83

1.81

1.83

CHADS2 Category

>=4

Multivariate hazard ratios (HRs) are displayed for patients with atrial fibrillation (AF)

An HR >1.0 indicates an increased risk of stroke in AF patients not treated with

ablation. HR s are displayed by CHADS2 risk scores. Stroke risk of AF ablation was

less than AF no ablation, even better than No AF.

0.50 0 1.50 2.00 2.5

0.86

0.84

0.870-12-3

Messages

1, AF ablation patients have a significantly lower risk ofstroke compared to AF patients who do not undergo ablation independent of baseline stroke risk score.

2, The lower risk persist across all age-related strata and independent of the CHADS2 risk score.

3,Limitationis : this was cohort study,no data available about anticoagulations strategy, compliance to anticoagulation,or physician adherenceto guidelines regarding anticoagulation.

But no suggestions of OAT discontinuation

Objectives： Evaluation of the safety of discontinuing oral

anticoagulation therapy (OAT)after apparently successful

pulmonary vein isolation.

Venice Bordeaux Philadelphia, Austin, Cleveland

Methods ：From 5 international EP centers, 3,355 patients, of whom 2,692 (79% male, mean age 57 11 years) discontinued OAT 3 to 6 months after ablation (Off-OAT group) and 663 patients (70% male, mean age 59 11 years) remained on OAT after this period (On-OAT group) were enrolled and analyzed.

The Risk of Thromboembolism and Need for Oral

Anticoagulation after Successful Atrial Fibrillation Ablation

(J Am Coll Cardiol 2010;55:735–43)

Off-OATgroup On-OAT group

Number of Pt. 2692 (male 79%) 663(male 70%)

mean age 57 ± 11 years 59 ±11 years

CHADS2 scores

0 1622 (60%) 155 (24%)

1 723 (27%) 261 (39%)

＞ 2 347 (13%) 247 (37%)

As a general rule, OAT was discontinued, regardless of

the CHADS2 score, if patients did not experience:

1)any recurrence of atrial tachyarrhythmia

(AF or atrial flutter/tachycardia longer than 1 min);

2) severe pulmonary vein stenosis

(pulmonary vein narrowing 70%)

3) severe left atrial (LA) mechanical dysfunction

(absence of A-wave on pulsed Doppler trans mitral

recording).

How did they decide discontinuation of OAT ?

The annual ischemic stroke

rate per 100 pt-yr

Off-OAT On-OAT

0.03 (95% [CI]: 0.004 to 0.114)

0.23 (95% CI: 0.047 to 0.662)

The annual rate for overall

thromboembolic and hemo

rrhagic strokes per 100 pt-yr

0.03

(95% CI: 0.004 to 0.114)

0.38 (95% CI: 0.123 to 0.881)

0.98 (95% CI: 0.523 to 1.678)

0.02 (95% CI: 0.001 to 0.088)

The annual majour hemorrage

rate per 100 patient-years

p=0.049

p<0.0001

p=0.002

Kaplan-Meier Event-Free Survival Estimates for Freedom From Post-Ablation

Thromboembolic and Hemorrhagic Strokes in the Off- and On-OAT Groups

On-OAT

Off-OAT

Results

CHADS2=0 CHADS2=1 CHADS2>2

off-OAT on-OAT off-OAT on-OAT off-OAT on-OAT

Patients No. 1622 155 723 261 347 247

Thrombo Emb. n (%) 1(0.06) 0 1(0.14) 1(0.38) 0 2(0.81)

Majour Hem. n (%) 0 1(0.64) 1(0.14) 2(0.8) 0 10(4)

The Incidence of Thromboembolic Events and Majour Hemorrhages according to CHADS2 score

in off- and On- OAT

In the Off-OAT group, only 2 of 2,692 (0.07%) patients experienced ischemic

stroke during follow-up. Interestingly, no patient with a CHADS2 risk score >2

developed TE after OAT discontinuation

(J Am Coll Cardiol 2010;55:735–43)

1, Discontinuation of OAT 3 to 6 months after successful AF

ablation had a similar incidence of TE in patients remained

on OAT.

2, It seems that the risk– benefit ratio favors the discontinuation

of OAT after successful AFablation even in patients at

moderate-high risk of TE based on CHADS2 score alone.

3, Limitations: Not randomized prospective study,

Scarce distribution of stroke( smaller number of on-OAT)

INR values were not available .

(J Am Coll Cardiol 2010;55:735–43)

Messages

Incidence of cerebral thromboembolic events

during long-term follow-up in patients

treated with transcatheter ablation for atrial fibrillationEuropace Advance Access published January 19, 2014

Europace doi:10.1093/europace/eut406

Aim; Evaluation of long-term thromboembolic (TE) and haemorrhagic

events incidence according to OAT strategy used after AF ablation.

Consecutive patients referred to Turin University centres between

2001 and 2009 for AF ablation were included in the AF Registry.

Seven hundred and sixty-six patients were enrolled and devided into

two groups after 3 months blank period of post ablation.

OFF-OAT : No AF recurrence and with CHADS2 ( 0 ,1). with ASA

ON -OAT: AF recurrence CHADS2 ( 0 ,1). and CHADS2 ( >= 2 )

regardless of the AF recurrence

Definition of recurrence:the presence of a sustained AF/atrial flutter lasting

>=30 s either symptomatically or documented by means of an ECG or 24 h

Holter monitoring.

Patients n=766OFF-OAT

n=499

ON-OAT

n=267p value

Thromboembolic Events 5 (1.0%) 6 (2.2%) p=0.145

Annual Ische. Stroke Rate 0.2/100pt.-years 0.43/100pt.-years p=0.50

Heamorrhagic Events 0(0%) 7 (2.6%) p=0.001

Cerebral thromboembolic events and haemorrhagic events

Seven hundred and sixty-six patients were followed for a median of 60.5 months.

TE events occurred in the both group with no differences, but heamorragc event.

When the study population was stratified by the CHADS2 score, a CHADS2

score ≥ 2 was significantly associated with the TE complications (P =0.047).

HAS-BLED score ≥ 2 was associated with a higher incidence of haemorrhagic

events (P= 0.038).

Results

Patients with a CHADS2 score of 0 or 1, could be divided by

CHA2DS2VASc score, into higher risk (score ≥ 2 )and lower risk

(score ≤ 1 ) group (p= 0.014). CHA2DS2VASc score might be better

system for risk stratification of patients after successful ablation.

Thromboembolic (TE) events in patients with a CHADS2

score of 0 or 1 stratified by the CHA2DS2VASc score.

Europace doi:10.1093/europace/eut406

1, Discontinuation of OAT 3 to 6 months after

successful AF ablation had a similar incidence of

TE in patients remained on OAT in especially

stratified by CHAD2 score <2.

2,CHADS2-VASC score system may starify

CHADS2 score mor precisely for identifing the low

risk group of TE after successfull ablation.

3, Limitations: Nonrandamized study, No data available about compliance to anticoagulation

(Information about INR , TTR)

Messages

Europace doi:10.1093/europace/eut406

Oral anticoagulation therapy after radiofrequency

ablation of atrial fibrillation and the risk of

thromboembolism and serious bleeding: longterm

follow-up in nationwide cohort of DenmarkEuropean Heart Journal Advance Access published November 3, 2014

Methods & Population:Linking Danish administrative registries, 4050

patients undergoing first-time RFA (2000–11) were enrolled.

The median age was 59.5 years ( IQR: 52.8–65.2); 26.5% were females.

They estimated patients whether on-OAC or off-OAC by prescription data

,divided into two groups and compared with stratification of risks of

thrombosis and bleeding..

Aim : To investigate the long-term risk of thromboembolism and serious

bleeding associated with oral anticoagulation (OAC)therapy beyond 3

months after radiofrequency ablation (RFA) of atrial fibrillation (AF).

CHA2DS2-VASc score, n (%)

0 (low risk) 1275 (31.5)

1 (intermediate risk) 1268 (31.3)

≥2 (high risk) 1507 (37.2)

HAS-BLED score, n (%)

≤1 (low risk) 2530 (62.5)

2 (intermediate risk) 1015 (25.1)

≥3 (high risk) 505 (12.5)

European Heart Journal doi:10.1093/eurheartj/ehu421

Univariate

Comparison

Multivariate

Comparison

Oral anticoagulation discontinuation was not associated with significantly increased

thromboembolic risk in low- or high-risk patients. Oral anticoagulation therapy was

associated with higher incidence rates of serious bleeding compared with OAC

discontinuation.

The incidence rates of thromboembolism and serious bleeding

according to OAC therapy

（N, number of events; IR, incidence rates per 100 person-years; HR, hazard ratio.）

Results

The 5-year cumulative incidence of thromboembolism

and serious bleeding according to OAC therapy.

Oral anticoagulation discontinuation was associated with 0.6% higher long-

term risk of thromboembolism, while risk of serious bleeding was decreased

by 1.8%.

OFF OAC

OFF OAC

0 1 2 3 4 5 0 1 2 3 4 5

ON OAC

ON OAC

(%)

4

3

2

1

0

(%)

4

3

2

1

0

0.6% 1.8%

(A) thromboembolism (B) serious bleeding

Years Years

European Heart Journal doi:10.1093/eurheartj/ehu421

1,Relatively low long-term risk of thromboembolism after

RFA ｗａｓ independent of CHA2DS2-VASc score.

2, Oral anticoagulation discontinuation was not associated

with significantly increased thromboembolic risk in low- or

high-risk patients

3, Serious bleeding risk associated with OAC therapy might

outweigh the benefit of OAC on thromboembolic risk

reduction.

4, Limitations: Not randomized study,

No information of discontinuation decision,

No information of INR or the quality of OAC therapy.

Messages

Study year Pt. No.

Study Form F/U periodOAC

Criteria of Stop OAC Results

A. Nataleet.al

2010 3359 Multi Ct.Non Rand.(Off vs On)

28±13MOAC: Warf.Swit ASA

Successful ablation Maintain At. Funct.Regardless Risk

Th. E. Off =OnRegardless Risk

Bleeding ON > Off

EB Saadet.al

2011 327 Single Ct.Non Rand(Off vs On)

46±17MOAC: Warf.Swit ASA

Successful ablationRegardless Risk(with Discontinue AA)

Th. E. Off =OnIn CHADS2=< 3

RAWinckleet.al

2013 108 Single Ct.Non RandIn OFF group(with Hx of stroke vs No Hx)

2.2±1.3YOAC: WarfOr NOAC

Successful ablationRegardless risk

TE. Off =OnRegardless RiskIn OFF group TE Hx = non HXBleeding ON >OFF

F Gaita et. al.

2014 766 Single Ct.Non RandOff vs On

62±62MOAC: Warf

Successful ablationCHADS2=<1

TE Off =OnLess than No AfCAH2DS2 –VASC usefulness for subd.

J-S Uhmet.al.

2014 721 Single Ct.Non RandOff vs On

18±12MOAC: WarfSwit ASA

Successful ablationRegardless risk

TE Off =OnBleeding ON = Off

D Karasoy

2014 4050 Nation Cohort

3.4±4.1YOAC: Warf

Not identified Th. E. Off =OnRegardless Risk

What we have known so far.

• Stroke rate in patients discontinued OAC after successful ablation is almost same as those continued OAC .

• Continuation of OAC expose patients hemorrhage more often than discontinuation.

• The power of evidence is not yet enough to make recommendation for discontinuation.

• The recurrence of AF is not easy identified in detail ( asymptomatic AF increase after abltaion etc. ).

Ansewr to the Question

We can tell that we may stop anticoagulation after

succefull ablation of AF, in the conditions of・・・・・

1, At 3 to 6months after ablation, no recurrence of AF

( by atndard ECG , Holtermonitoring , or self symptoms

whatever)

2, The rsik of stroke must be lower CA2DS2-VASC score

less than 2, preferablly. In such case stroke risk will be

lower even AF recurrence.

3, After more evidence we will be able to stop OAC after

successful ablation of AF with confidence.

The consensus of HRS/EHRA/ECAS Expert 2012

Systemic anticoagulation should be continued indefinitely

in patients with a high risk for stroke as estimated by

currently recommended schemes (CHADS2 or

CHA2DS2VASc), and especially in those who are 75 years

of age or older or have had a prior stroke or TIA.

Heart Rhythm, Vol 9, No 4, April 2012

(1) Recurrences of AF are common both early

and late following AF ablation,

(2) Asymptomatic AF is common following AF ablation,

(3) AF ablation destroys a portion of the atria and the impact

of this on stroke risk is uncertain,

(4) There have been no large randomized prospective trials

that have assessed the safety of stopping

anticoagulation

in this patient population, and

Thank you for your attention!