LES TROUBLES DU RYTHME:

MEDICAMENTS OU PACEMAKER?

LESQUELS

Prof L DE ROY

QUELS CHOIX POUR LA PERSONNE AGÉE ?

• 1. Les antiarythmiques (AAD)• 2. Les anticoagulants (OAC)• 3. Les pacemakers (PM)• 4. Les défibrillateurs (DAI/ICD)• 5. La resynchronisation (CRT)

LES TROUBLES DU RYTHME:

MEDICAMENTS OU PACEMAKER?

LESQUELS

Les Arythmies auriculairesLes Arythmies auriculaires

4Go AS. et al. JAMA 2001;285:2370-2375.

0.1 0.2 0.4 0.9 1.01.7 1.7

3.0 3.4

5.0 5.0

7.3 7.2

10.39.1

11.1

0

2

4

6

8

10

12

< 55 55-59 60-64 65-69 70-74 75-79 80-84 ≥ 85

Age (years)

Prev

alen

ce %

AF Prevalence Increases with Age

Men

Women

Guidelines ESC 2010 EHJ

Classification des principaux antiarythmiques: Vaughan-WilliamsClassification des principaux antiarythmiques: Vaughan-Williams

Classe I Classe II Classe III Classe IV Autres ADisopyramide (Rythmodan ) β-bloquants Sotalol (Sotalex) Verapamil (Isoptine) Digitale(Lanoxin)

Quinidine (Kinidine-Durettes) Amiodarone Diltiazem (Tildiem) Adénosine (Cordarone) (Adenocor)

(Striadyne )

Procainamide (Pronestyl)

B

Lidocaine (Xylocaïne )

Mexiletine (Mexitil )

CPropafenone (Rytmonorm )

Flecaïnide (Tambocor )

(Apocard R )

Cibenzoline (Cipralan )

Dronedarone (Multacq )

Guidelines ESC 2010 EHJ

ANTIARYTHMIQUES et FONCTION RENALE

L’isolation des veines pulmonaires

JCE 2012N= 103 / 2754

Guidelines for the management of AF EHJ 2010

LES ANTICOAGULANTS

Guidelines for the management of AF EHJ 2010

LES ANTICOAGULANTS

BAFTA TRIAL Lancet 2007

Coumariniques vs Aspirine dans la FA de la personne âgée > 75 ans

n: 973

Guidelines for the management of AF EHJ 2010

Et le risque hémoragique ?

RE-LY

Les Nouveaux

Antithrombines:

Dabigatran (Pradaxa)

Anti Xa:

Rivaroxaban (Xarelto) Apixaban (Eliquis)

• Efficacité et risques hémorragiques identiques• Pas de contrôles réguliers• Courte durée d’action et délai bref• Prix ?

DABIGATRAN

Les Bradycardies

LA DYSFONCTION SINUSALE

Choix du Pacemaker : AAI ?VVI ?DDD ?

SINUS NODE DISEASE

CTOPP: n: 2568 mean age: 73 ± 10

AAI

DDD

VVIOR

SINUS NODE DISEASE

DANPACE (2011): n: 1415

mean age: 73

AAIR

DDDR

OR

PACEMAKER CONFIGURATION: VVI or DDD?

LES BLOCS AURICULO-VENTRICULAIRES

LES BLOCS AURICULO-VENTRICULAIRES

UKPACE NEJM 2005> 70y

AM H J 2003N= 1588 ≥ 80 y

ICD

LES DÉFIBRILLATEURS

CIRC 2009

ALL CAUSE MORTALITY

N= 965

COÛT EFFICACITÉ

Chan CIRC 2009Markov model

L Basta AJGC 2006

• Evaluation éthique au cas par cas• Consentement éclairé• Problèmes de fin de vie

Contre-indications

…..(07-2011)

LA RESYNCHRONISATION CRT

54.5%

39.3%

58.6%

Control N=145

<0.0010.55 (0.36-0.84)22.9%All cause mortality

0.00010.51 (0.36-0.73)32.5%All cause mortality or un-planned HF hospitalization

0.0150.67 (0.48-0.92)43.3%All cause mortality or un-planned CV hospitalization

P-valueHazard ratio

(95% CI)CRT

N=157

CARE-HF: Reductions in morbidity and mortality in elderly CRT patients

• CARE-HF sub-population of patients aged ≥70 years• CRT reduced mortality and morbidity versus medical treatment

alone (MT) in elderly patients

Mabo P et al. Circulation 2008;118:S949 (Abstract 8450). [CARE-HF, a Medtronic sponsored study]

n = 15381

Yancy C et al. J Cardiac Fail 2007;13(suppl):S158. Abstract 290.

Findings from IMPROVE HF:Underutilization of CRT in Elderly

• Underutilization of CRT is exaggerated in eligible elderly HF patients

Patients Receiving Recommended HF Therapies by Age Tertiles at Baseline (All Patients)

89,9

39,7

80,385,9

42,9

73,181,4

33,6

84,6

ACEI/ARB BetaBlocker

CRT (CRT-D/CRT-P)

Pat

ient

s (%

)

Age</=64Age 65-76Age>76

CARE-HF: CRT improves QoL and cardiac function/status in the elderly

Minnesota Living w/ HF

4229 27

44 38 35

Baseline 3 Mo. 18 Mo.

• CARE-HF sub-population of patients aged ≥70 years

• Presented at AHA 2008

1. Laviolle et al. Circulation 2008;118:S950b (Abstract 48540). 2. Leclercq C, et al. Circulation 2008;118:S619b (Abstract 826)

P=0.50 P<0.001 P=0.001

■ CRT On ■ CRT Off

LVEF

26%37%

26% 31%

Baseline 18 Mo.

LVESV (mL)

217124

223 182

Baseline 18 Mo.

P<0.001P=0.53

P=0.40 P<0.001

1

2

2

MIRACLE study program demonstrates CRT benefit in elderly patients

5,2%

3,0%4,0%

1,4%0,6%0,8%

Age <65 Age 65-75 Age >75

• MIRACLE + MIRACLE ICD• Mean change at 6 months• 839 patients: 368 < 65 years; 297 65 – 75 years; 174 > 75 years• No evidence of increased adverse event rates in most elderly group

Change in NYHA

-0,8 -0,8 -0,8-0,5 -0,5 -0,4

Age <65 Age 65-75 Age >75

LVESV Change (mL)

-43 -23-8-18 -1

4

Age <65 Age 65-75 Age >75

Absolute LVEF Change

Kron et al.J Interv Card Electrophysiol:2009 Jan 19. [Epub ahead of print Jan 19]

■ CRT On ■ CRT Off

P<0.001 P=0.002 P=0.004

P=0.008P<0.001

P=0.002

P<0.001P<0.001

P=0.06

Do elderly patients benefit from CRT?

• Recent analyses of randomized controlled trials provide data on the efficacy and safety of CRT in the elderly– Extended survival, improved quality of life, and

improved cardiac function and status

• Guidelines are the same for elderly patients1

– Life expectancy >1 year

• CRT-P may be considered to extend survival and improve quality of life in select elderly patients where defibrillation is not desired

1. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities. J Am Coll Cardiol, 2008; 51:2085-2105.

Number Needed to Treat To Save A LifeNNTx years = 100 / (% Mortality in Control Group – % Mortality in Treatment Group)

25

147,5

3 411 9

14 1420

2529 29

37

56

0

10

20

30

40

50

60

CARE-HF MUSTT MADIT MADIT II AVID SCD-HeFT SAVE CIBIS II MERIT HF Amiodorone HOPE

CR

T

CR

T-D

CR

T

ICD

Drugs

CRT

Adapted from Auricchio A, Abraham W. Circulation 2004; 109; 300-307.

(1Yr) (3Yr) (5Yr) (2.4Yr) (3Yr) (3Yr) (4Yr) (0.8Yr) (3.5Yr) (1Yr) (1Yr) (1.5Yr) (2Yr) (4 Yr)

COMPANION COPER-NICUS

CAP-RICORN

COMPANION: CRT-D and CRT-P Incremental Cost-Effectiveness Ratios

• 2-year analysis of COMPANION study

• CRT-P ICER = $19,600 per Quality-Adjusted Life-Year (QALY)

• CRT-D ICER = $43,000 per QALY– Essentially getting two

therapies for one price• Well below generally accepted

benchmarks for therapeutic interventions of $50,000 - $100,000 per QALY

Feldman AM, et al. J Am Coll Cardiol 2005; 46: 2311 – 2321. [COMPANION sponsored by Guidant]

$19.600

$43.000

$0

$25.000

$50.000

$75.000

CRT-P CRT-D

Benchmark $50,000/QALY

Incremental Cost-Effectiveness Ratios of CRT-P/CRT-D ($/QALY)

Effect of Starting Age and Device Longevity on Cost per QALY – Base case

0

10,000

20,000

30,000

40,000

50,000

60,000

70,000

80,000

55 60 65 70 75Age at Starting Treatment

Incr

emen

tal C

ost P

er Q

ALY

Gai

ned

€

CRT+MT vs MT CRT+ICD+MT vs CRT + MT CRT+ICD+MT vs MT

8 Years

5 Years7 Years

Conclusions

• Long-term treatment with CRT-P appears highly cost-effective compared to medical therapy for any starting age

• The cost effectiveness of CRT-ICD compared to CRT-P is conditional on patient life expectancy and device longevity

• Where device longevity is adequate, and patient life expectancy with CRT-P is sufficient, CRT-ICD may also be considered cost-effective

Ermis C Europace 2007Death: 22 vs 14%

≥ 75 Y

INSUFFISANCE CARDIAQUE

AF

Results: Baseline Practice Characteristics

• By Age Tertiles (≤64y, 65-76y, >76y)– Younger patients more likely to attend multispecialty, hospital-

based, and transplant-affiliated outpatient clinics (P<.001 all comparisons).

– Younger patients also more likely to receive care from outpatient practices with a dedicated heart failure clinic, and with electrophysiologists on staff (P<.001 all comparisons).

• By Sex– Women were more likely than men (14.1% vs. 12.7%; P=.025) to

attend a transplant-affiliated outpatient clinic.– More women than men received care at practices with a device

clinic (82.8% vs. 80.4%; P<.001)

Yancy CW, et al. Am Heart J 2009;157:754-62

Baseline Patient Characteristics by Age Tertile

<.0011.31.21.1Creatinine, median, mg/dL<.001547383254BNP, median, pg/mL<.001136130110QRS duration, median, ms

<.00164%64%58%Hypertension history

<.00141%32%20%Atrial fibrillation history

P>76 y

n=4,79165-76 yn=5,176

≤64 yn=5,307Characteristic

<.00167%73%73%Male<.00173%71%53%Ischemic etiology

<.00129%38%35%Diabetes

<.00142%43%34%Prior MI<.00135%37%22%CABG<.001252525LVEF, median, %

<.001120120120SBP, median, mm Hg<.001262218BUN, median, mg/dL

Yancy CW, et al. Am Heart J 2009;157:754-62

Results: Older Patients Less Likely to Receive Guideline-Indicated HF Therapies

84%90%

46%

71%

39%

52%

66%

80%86%

34%

71%

43%

57%61%

73%

81%

27%

68%

34%

43%

57%

0%

25%

50%

75%

100%< 65y 65-76y >76y

ACEI/ARB Beta-blocker AldosteroneAntagonist

Anticoag.for Atrial Fib.

ICD HFEducation

Cardiac Resynch.

P<.001 P<.001

P<.001

P=.180

P=.028

P<.001P<.001

Elig

ible

pat

ient

s w

ith t

reat

men

t (%

)

Yancy CW, et al. Am Heart J 2009;157:754-62

Results: Significant Differences when Stratified by Age and Sex

47%36% 42%43%

30%37%

0%

50%

100%< 65y 65-76y >76y

Cardiac Resynchronization

Males Females

P=.124 P=.010

50%44%32%34% 27%26%

0%

50%

100%< 65y 65-76y >76y

Males Females

Aldosterone Antagonist

P<.001 P<.001

48%53% 50%59%

32%48%

0%

50%

100%< 65y 65-76y >76y

ICD or CRT-D

Males Females

P<.001 P<.001

• When stratified by age and sex, differences in delivery of guideline-indicated care most striking for:– Aldosterone antagonist;– Cardiac resynchronization (CRT or

CRT-D)– ICD (ICD or CRT-D)

Yancy CW, et al. Am Heart J 2009;157:754-62

Older and Female Patients Less Likely to Receive Some Care Measures

Adjusted odds ratio with 95% CI displayed

Care Measure

ACEI/ARB

ß-Blocker

Aldosterone Antagonist

Anticoagulation for AF*

Cardiac Resynchronization*

HF Education

ICD/CRT-D*

By Increasing Age

0,87

0,85

0,81

0,99

0,88

0,94

0,93

0,1 1 10

By Sex

1,14

0,93

0,79

1,44

1,04

1,42

1,16

0,1 1 10

FemalesMoreLikely

Conformity to Care Measures

MalesMoreLikely

YoungerMoreLikely

OlderMoreLikely

* Significant age and sex interaction

Yancy CW, et al. Am Heart J 2009;157:754-62

(per 10 years)

P<.0001

P<.0001

P<.0001

P=.0233

P<.0001

P=.0023

P=.0199

P=.2400

P=.0358

P=.0001

P=.7702

P<.0001

P=.0010

P=.7767

Conclusions

• Females and the more elderly are less likely to receive certain guideline-recommended evidence-based heart failure treatments in the outpatient setting– Older patients received less pharmacologic therapy, less device

therapy, and less heart failure education.

– Women received less heart failure education and less device therapy.

Yancy CW, et al. Am Heart J 2009;157:754-62

Aspirine: less effect after 75 y

NEJM 2008

SSSAVB

n= 2568

CTOPP

Age moyen: 86.2 ansn: 149

Comparable to data from younger but higher 30 d all cause mortality

JICE 2011

DANPACE 2011n = 1415

AFDEATH

MOST Total Mortality or Stroke

0 6 12 18 24 30 36 42 48 54 600.00

0.10

0.20

0.30

0.40

0.50

Months

Even

t Rat

e

P = 0.48Adjusted P = 0.32

Ventricular pacing

Dual-chamber pacing

Lamas G, et al. N Engl J Med 2002; 346: 1854-62.

No. at risk:Ventricular pacing

Dual-chamber pacing 996 934 897 813 678 557 431 320 218 125 391014 963 930 833 693 555 431 328 214 120 28

MOST MOST ConclusionsConclusions

• In patients with SND, dual-chamber pacing In patients with SND, dual-chamber pacing (versus single-chamber ventricular pacing) (versus single-chamber ventricular pacing) REDUCESREDUCES newly diagnosed and chronic atrial newly diagnosed and chronic atrial fibrillationfibrillation, reduces the signs and symptoms of , reduces the signs and symptoms of heart failure, and slightly improves quality of heart failure, and slightly improves quality of life.life.

• Dual-chamber pacing did Dual-chamber pacing did NOTNOT improve the rate improve the rate of the primary endpoint of of the primary endpoint of mortality or freedom mortality or freedom from strokefrom stroke..

SINUS NODE DISEASE

MOST: n: 2010mean age: 74 (67-80)

NS

DDD

VVI

OR

Pacemaker ConfigurationsVVI

Indications

The combination of AV block and chronic atrial arrhythmias (particularly atrial fibrillation).

Pacemaker ConfigurationsDDD

♀ C. 70 y: recurrent syncope aVR

aVR

aVF

V1

V2

V3

V4

V5

V6

I

II

III

I

V

•AAI pacing 70/min•CAVB: 12 s asystole•Suspected level of block: nodal

♀ H. 71 y: syncope •ECG: Normal (PR 158 ms, QRS 88ms)

• CAVB :11 s asystole

•Supposed level of block: nodal

Les stimulateurs cardiaques

Battery

Connector

Hybrid

Telemetry antenna

Output capacitors

Reed (Magnet) switch

Clock

Defibrillation protection

Atrial connector

Ventricular connector

Resistors

Anatomy of a Pacemaker

Kaszala K, Ellenbogen K AJGC 2006

CIRC 2009

ICD AND AGE

CIRC 2009

N= 965

PENGO THROMBOSIS AND HEMOSTASISI 2011

PENGO THROMBOSIS AND HEMOSTASISI 2011