TRIAL ON VT TREATMENT -...

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q  IICCDD iinn pprriimmaarryy pprreevveennttiioonn

Primary prevention § MADIT (1) § CABG-Patch (2) § CAT (1) § MUSTT (3) § AMIOVIRT (1) § MADIT II (1) § SCD-HeFT (4) § DINAMIT (5) § DEFINITE (5) § IRIS

Inserire bibliografia

MADIT §  MADIT: 1990 – 1995

" RCT* multicenter with ICD vs. antiarrhythmic drugs " 32 centers/196 pts, follow-up 27 months " Inclusion criteria : MI ≥ 3 weeks before enrolment, EF ≤ 35 % " Other risk factors: NSVT and inducible VT inducibile " Results:

Mortality: 16% in ICD group vs. 39% in standard therapy group . Aboslute risk reduction 23%

*Studio clinico randomizzato Moss AJ et al. NEJM 1996;335:1933-40

§  DINAMIT: 1998 – 2002

" RCT multicenter: ICD vs. OMT " 73 centers/674 pts, follow-up 30 months " Inclusion criteria: 6 - 40 days after IM, LVEF ≤ 35%

§ Results: " Mortality:7,5% ICD group vs. 6,9% in OMT group, not

significant

DINAMIT

Hohnloser Kuck, Connolly et al. NEJM 2004;351:2481-88

MADIT II

§  MADIT II: 1997 – 2001

" RCT multicenter ICD vs. OMT " 76 centers/1.232 pts, follow-up 20 months " Inclusion criteria: previous MI, EF ≤ 30%

§ Results: § 14,2% ICD vs. 19,8 OMT. § Absolute risk reduction 5,6%. p=0,007

Moss JA et al. NEJM 2002;346:887-83

MADIT II Study design

§ Randomization: ICD vs. without ICD (ratio 3:2) § Sequential design

•  OPT •  ICD

•  OPT

+

(n = 490)

(n = 742)

Randomization

NEJM 2002;346: fig. 2, pag. 880

Tempo (anni)

Prob

abili

tà d

i sop

ravv

iven

za

Curve di Kaplan-Meier che indicano la probabilità di sopravvivenza nel gruppo trattato con ICD + OPT e in quello trattato con OPT soltanto.

MADIT II Survival

Mortality reduction in MADIT II is the consequence of SCD reduction

MADIT II: SCD

SCD OPT: 10,0% ICD: 3,8%

Anni

Prob

abili

tà c

umul

ativ

a di

mor

te c

ardi

aca

impr

ovvi

sa

N. a rischio

ICD

OPT

CONV

MMAADDIITT IIIISSCCDD MMoorrttaalliittyy

§ Prematurely suspended " median Follow-up 20 months

§ Mortality reduction 31% § Hazard ratio = 0,69, p = 0,016 " Absolute reduction = 5,6 %

§ Determined FDA indication

MADIT II Results

Hazard ratio

(EF ≤ 0,35, NSVT, EP+)

(Aborted SCD)

(EF ≤ 0,40, NSVT, EP+)

(Previous MI & EF ≤ 0,30)

ICD better

MMAADDIITT IIIINNeell ccoonntteessttoo ccoonn ggllii ssttuuddii ssuullll’’IICCDD

The sudden Cardiac death in Heart Failure Trial (SCD-HeFT 1997-2001) A trial designed to evaluate the effect of amiodarone or implantable Cardioverter-Defibrillator for congestive Heart Failure The New England Journal of Medecine (January 20, 2005)

Bardy GH et al. NEJM 2002;346:877-83

SCD-HeFT

§ 2.500 pts §  Ischemic or non ischemic cardiomyopathy § Primary Endpoint : total Mortality in 2,5 years of FU § Secondary Endpoint :

§ Arrhythmic Mortality vs. non arrythmic § All cause mortality and HF hospitalization § Quality of life….

SCD-HeFT Disegno dello studio

§  HF NYHA II/III §  EF ≤ 35% §  CHF ≥ 3 mesi §  Age ≥ 18 year §  No cardiac arrest or sustained VT documented

SSCCDD--HHeeFFTTEElleeggiibbiilliittyy

Am J Cardiol 1999;83: fig. 1, pag. 94D

1

2 •  OMT •  ICD +

•  OMT •  Placebo

•  OMT •  Amiodarone +

2

§ Multicenter (148) § Randomization 2.521 pts in 3 groups

+ Placebo

Randomization

SCD-HeFT Study design SCD-HeFT

ICD

Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl. J Med. 2005; 352:225-237. © 2005 Massachusetts Medical Society. All rights reserved.

§  23% total mortality reduction in ICD (p=0,007)

Mortalità secondo l’analisi intention-to-treat Hazard ratio (IC 97,5%)

1,06 (0,86-1,30) 0,77 (0,62-0,96)

P 0,53 0,007

182 decessi; percentuale a 5 anni

0,289)

Amiodarone (240 decessi; % a

5 anni, 0,340)

FU months

Terapia con ICD

SSCCDD--HHeeFFTTEEnnddppooiinntt pprriimmaarriioo:: MMoorrttaalliittàà ppeerr qquuaalluunnqquuee ccaauussaa

05

101520253035404550

SCD-HeFT 5-Year Mortality Rate Ischemic vs. Non-Ischemic

41.7% 43.2%

21.4% 25.8% 27.9%

35.9%

Ischemic Non- Ischemic



Amiodarone Placebo ICD

Mor

talit

y R

ate

Bardy GH. N Engl J Med. 2005;352:225-237.

No. at Risk Amiodarone 601 563 536 378 222 76 Placebo 594 563 522 367 218 72 ICD 566 550 531 371 236 80

SCD-HeFT Mortality Rate NYHA Class II Patients

Months of Follow-Up

Mor

talit

y R

ate

48 36 24 12 0

Amiodarone Placebo ICD 0.4

0.3

0.2

0.1

0.0 60

Hazard Ratio (97.5% Cl) P-Value Amiodarone vs. Placebo 0.85 (0.65 - 1.11) 0.17 ICD vs. Placebo 0.54 (0.40 - 0.74) < 0.001


0.5

0.6

No. at Risk Amiodarone 244 209 179 106 58 21 Placebo 253 234 202 138 86 17 ICD 263 228 202 130 68 23

SCD-HeFT Mortality Rate NYHA Class III Patients

Months of Follow-Up

Mor

talit

y R

ate

48 36 24 12 0


60

Hazard Ratio (97.5% Cl) P-Value Amiodarone vs. Placebo 1.44 (1.05 - 1.97) 0.010 ICD vs. Placebo 1.16 (0.84 - 1.61) 0.30


0.4

0.3

0.2

0.1

0.0

0.5

0.6

0

10

20

30

40

50

60

SCD-HeFT 5-Year Mortality Rate NYHA Class II vs. III

26.4% 32%

48.4% 52.8%

45.6%

20%

NYHA II NYHA III NYHA II NYHA III NYHA II NYHA III


Mor

talit

y R

ate


SCD-HeFT Mode of Death Cause of Death Amiodarone

N = 845 Placebo N = 847

ICD N = 829

Cardiac 19% 20% 15%

Tachyarrhythmia 9% 11% 4%

Bradyarrhythmia < 1% < 1% < 1%

Heart Failure 8% 8% 9%

Nonarrhythmic 1% < 1% 1%

Packer DL. Heart Rhythm 2005. May;2 (1suppl):AB20-2.

SCD-HeFT Tachyarrhythmia Deaths

Cause of Death Amiodarone N = 845

Placebo N = 847

ICD N = 829

Tachyarrhythmia 9% 11% 4%

ICD therapy reduced tachyarrhythmia deaths by 60%

Packer DL. Heart Rhythm 2005. May;2 (1suppl):AB20-2.

SCD-HeFT Conclusions •  ICD therapy provided the largest mortality

reduction in NYHA Class II patients •  Surviving patients had improvements in

their heart failure condition over time. Good drug management likely contributed to this improvement.

•  Compared to other CV therapies, ICDs are a cost-effective therapy

Mortality reduction: Summary

PPrriimmaarryy pprreevveennttiioonn ttrriiaall

Primary prevention trials Conclusions

§ Primary prevention trials identified pts at risk § 2 landmark studies MADIT II and SCD-HeFT

contributed to define pts at risk:

§ post MI pts § HF pts With reduced LVEF

§ Summarizing, prophylactic ICD reduces SCD in high risk pts in OMT:

§ Previous aborted SCD (VT o VF) § Previous MI with LVEF ≤ 30% § HF pts (NYHAII/III) with LVEF ≤ 35%

Trials Conclusions

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