“Non servono gli antiaritmici?”

Prof Luigi Padeletti

Università di Firenze

Heart Failure & Co.

Caserta, 29-30 aprile 2011

Sommario degli Sommario degli studi sul trattamento studi sul trattamento farmacologicofarmacologico

Sospeso per Sospeso per numero numero eccessivo di decessieccessivo di decessi nel nel braccio di studio braccio di studio

Encainide, Encainide, flecainide/ placeboflecainide/ placebo

14981498CAST-ICAST-I11

Nessuna variazioneNessuna variazione rispetto rispetto alla mortalitalla mortalitàà globale globale

Amiodarone/PlaceboAmiodarone/Placebo12001200CAMIATCAMIAT66

Nessuna variazioneNessuna variazione rispetto rispetto alla mortalitalla mortalitàà globale globale

Amiodarone/PlaceboAmiodarone/Placebo15001500EMIATEMIAT55

Mortalità elevataMortalità elevata in ambedue in ambedue i braccii bracci

EPS-guidato/Holter-EPS-guidato/Holter-guidatoguidato

486486ESVEMESVEM44

Sospeso per Sospeso per numero numero eccessivo di decessieccessivo di decessi nel nel braccio di studio braccio di studio

d-sotalolo/Placebod-sotalolo/Placebo546546SWORDSWORD33

Nessuna variazioneNessuna variazione rispetto alla mortalitrispetto alla mortalitàà globale globale

Amiodarone/PlaceboAmiodarone/Placebo674674CHF-STATCHF-STAT22

•RisultatoRisultatoDisegno dello Disegno dello studiostudio

PazientiPazientiStudioStudio

1 Echt, et al. N Engl J Med. 1991;324:781–8.2 Singh, et al. N Engl J Med. 1995;333:77–82 (supported by Sanofi & Wyeth).3 Waldo A.L. The Lancet; 1996;348:7–12. (supported by Bristol-Myers Squibb).

4 Mason J.W. N Engl J Med. 1993;329(7):452–8. (Supported by Bristol-Myers Squibb, Knoll Pharmaceutical, Boehringer-Ingelheim, Parke-Davis, and Ciba-Geigy). 5 Julian D.G. The Lancet. 1997;349:667–74.(Supported by Sanofi)6 Cairns J.A. The Lancet. 1997;349:675–82.

Implanted Standby Defibrillators

“ In fact, the implanted defibrillator system represents an imperfect solution in search of a plausible and practical application.”

Circulation, Volume XLVI, October 1972

Bernard Lown and Paul Axelrod

1 The AVID Investigators. N Engl J Med. 1997;337:1576-83.2 Kuck K. Circ.2000;102:748-54.3 Connolly S. Circ. 2000;101:1297-1302.

0

20

40

60

80

AVID CASH CIDS1 2 3

31%28%

20%

% M

ort

alit

y R

edu

cti

on

w/

ICD

Rx

Secondary Prevention Trials:Secondary Prevention Trials: Reduction in Overall Mortality with ICD Therapy Reduction in Overall Mortality with ICD Therapy

3 Years 3 Years 3 Years

1 The AVID Investigators. N Engl J Med. 1997;337:1576-83.2 Kuck K. Circ.2000;102:748-54.3 Connolly S. Circ. 2000;101:1297-1302.

0

20

40

60

80

AVID CASH CIDS

Overall Death

Arrhythmic Death

1 2 3

31%

56%

28%

59%

20%

33%

% M

ort

alit

y R

edu

cti

on

w/

ICD

Rx

Secondary Prevention Trials:Secondary Prevention Trials: Reduction in Mortality with ICD Therapy Reduction in Mortality with ICD Therapy

3 Years 3 Years 3 Years

1 Moss AJ. N Engl J Med. 1996;335:1933-40.2 Buxton AE. N Engl J Med. 1999;341:1882-90.3 Moss AF. N Engl J Med. 2002;346:877-83.

0

20

40

60

80

MADIT MUSTT MADIT-II1 2 3

54% 55%

31%

Primary Prevention Post-MI Trials: Primary Prevention Post-MI Trials: Reduction in Overall Mortality with ICD TherapyReduction in Overall Mortality with ICD Therapy

27 Months 39 Months 20 Months

% M

ort

alit

y R

edu

cti

on

w/

ICD

Rx

1 Moss AJ. N Engl J Med. 1996;335:1933-40.2 Buxton AE. N Engl J Med. 1999;341:1882-90.3 Moss AF. N Engl J Med. 2002;346:877-83.4 Moss AJ. Presented before ACC 51st Annual Scientific Sessions, Late Breaking Clinical Trials, March 19, 2002.

0

20

40

60

80

MADIT MUSTT MADIT-II

Overall Death

Arrhythmic Death

1 2 3, 4

54%

75%

55%

73%

31%

61%

Primary Prevention Post-MI Trials: Reduction in Primary Prevention Post-MI Trials: Reduction in Mortality with ICD TherapyMortality with ICD Therapy

27 Months 39 Months 20 Months

% M

ort

alit

y R

edu

cti

on

w/

ICD

Rx

0

20

40

60

80

MADIT MUSTT MADIT-II

0

20

40

60

80

AVID CASH CIDS

1 Moss AJ. N Engl J Med. 1996;335:1933-40.2 Buxton AE. N Engl J Med. 1999;341:1882-90.3 Moss AJ. N Engl J Med. 2002;346:877-834 The AVID Investigators. N Engl J Med. 1997;337:1576-83.5 Kuck K. Circ. 2000;102:748-54.6 Connolly S. Circ. 2000:101:1297-1302.

ICD mortality reductions in ICD mortality reductions in primary prevention trialsprimary prevention trials

are equal to or greaterare equal to or greaterthan those in secondarythan those in secondary

prevention trials.prevention trials.

1 2

4 65

Reductions in Overall Mortality with ICD TherapyReductions in Overall Mortality with ICD Therapy

54% 55%

31%

27 months 39 months 20 months

31%28%

20%

% M

ort

ali

ty R

ed

uc

tio

n w

/ IC

D R

x%

Mo

rta

lity

Re

du

cti

on

w/

ICD

Rx

3 Years 3 Years 3 Years

3

0

20

40

60

80

MADIT MUSTT MADIT-II

Overall Death

Arrhythmic Death

0

20

40

60

80

AVID CASH CIDS

Overall Death

Arrhythmic Death

1 Moss AJ. N Engl J Med. 1996;335:1933-40.2 Buxton AE. N Engl J Med. 1999;341:1882-90.3 Moss AJ. N Engl J Med. 2002;346:877-834 Moss AJ. Presented before ACC 51st Annual Scientific Sessions,

Late Breaking Clinical Trials, March 19, 2002.5 The AVID Investigators. N Engl J Med. 1997;337:1576-83.6 Kuck K. Circ. 2000;102:748-54.7 Connolly S. Circ. 2000:101:1297-1302.

ICD mortality reductions in ICD mortality reductions in primary prevention trialsprimary prevention trials

are equal to or greaterare equal to or greaterthan those in secondarythan those in secondary

prevention trials.prevention trials.

1 3, 42

5 76

Reductions in Mortality with ICD TherapyReductions in Mortality with ICD Therapy

54%

75%

55%

76%

31%

61%

27 months 39 months 20 months

31%

56%

28%

59%

20%

33%

% M

ort

ali

ty R

ed

uc

tio

n w

/ IC

D R

x%

Mo

rta

lity

Re

du

cti

on

w/

ICD

Rx

3 Years 3 Years 3 Years

Reason for treatment with AADs in ICD recipients

Prognostic importance of defibrillator shocks in patients with

heart failure

Benefits of adjuvant AADs in ICD patients

Post-infartoPost-infarto

Betabloccanti: Effetti sulla mortalitàBetabloccanti: Effetti sulla mortalità

YUSUF SYUSUF S.. et al. Prog Cardiovas Dis, 1985; 17: 335-371 et al. Prog Cardiovas Dis, 1985; 17: 335-371

BETABLOCCANTIBETABLOCCANTI PLACEBOPLACEBO RIDUZIONERIDUZIONE

934/12438934/12438

(7.5%)(7.5%)

288/8115288/8115

(3.5%)(3.5%)

1124/118601124/11860

(9.5%)(9.5%)

401/7706401/7706

(5.2%)(5.2%)

- 21%- 21%

- 33%- 33%

Mortalità TotaleMortalità TotaleMortalità TotaleMortalità Totale

Morte ImprovvisaMorte ImprovvisaMorte ImprovvisaMorte Improvvisa

26 trials > 24.000 pts26 trials > 24.000 pts

Clinical Trial summarizing Benefits of AADs

Clinical Trial summarizing Benefits of AADs

OPTIC Trial

Side Effects of Beta-Blockers Side Effects of Beta-Blockers could be Beneficialcould be Beneficial

Conclusions

Adjunctive AAD therapy often is necessary in many patients with ICDs for control of recurrent ventricular tachyarrhythmias and prevention of ICD shocks.

Conclusions

Given the scarsity of safe and effective AADs for this indication, the decision of when to start an AAD in the patient with an ICD must be individualized.

Conclusions

If AAD therapy is initiated, the potential for drug-related toxicities and device interactions must be recognized and anticipated.